CN112255418A - Application of plasma protein combination in preparation of product for predicting low-dose radiation exposure dose - Google Patents

Application of plasma protein combination in preparation of product for predicting low-dose radiation exposure dose Download PDF

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CN112255418A
CN112255418A CN202011123222.4A CN202011123222A CN112255418A CN 112255418 A CN112255418 A CN 112255418A CN 202011123222 A CN202011123222 A CN 202011123222A CN 112255418 A CN112255418 A CN 112255418A
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animal
dose
plasma
selp
content
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CN112255418B (en
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付汉江
葛常辉
郑晓飞
朱捷
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Institute of Pharmacology and Toxicology of AMMS
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Institute of Pharmacology and Toxicology of AMMS
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6863—Cytokines, i.e. immune system proteins modifying a biological response such as cell growth proliferation or differentiation, e.g. TNF, CNF, GM-CSF, lymphotoxin, MIF or their receptors
    • G01N33/6869—Interleukin
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/40—Disorders due to exposure to physical agents, e.g. heat disorders, motion sickness, radiation injuries, altitude sickness, decompression illness

Abstract

The invention discloses application of a plasma protein combination in preparing a product for predicting low-dose radiation exposure dose. The invention provides an application of a substance for detecting IL-5, IL-12p40 and/or SELP content in blood plasma: preparing a product for predicting a low dose radiation exposure dose; a product is prepared for predicting the number and/or duration of low dose radiation exposures. The plasma protein combination discovered by the invention can be used as an index for predicting long-term low-dose radiation accumulated dose, and further provides the application of the plasma protein combination in predicting the long-term low-dose radiation accumulated dose. The application is of great significance in diagnosing cumulative radiation dose to a radiologist threatened by long-term low-dose radiation.

Description

Application of plasma protein combination in preparation of product for predicting low-dose radiation exposure dose
Technical Field
The invention relates to the field of biotechnology, in particular to application of a plasma protein combination in preparation of a product for predicting low-dose radiation exposure dose.
Background
The influence of long-term low-dose radiation on human health is always a concern, occupational personnel such as medical X-ray diagnosis, interventional therapy, radiotherapy, nuclear medicine, nuclear industry, nuclear mining, industrial flaw detection and the like are engaged in, and the aspects of blood, nerves, digestive system, skin, eye lens, heredity and the like are easily influenced by radiation to different degrees during long-term low-dose irradiation, but specific influenced tissues, parts, damage degrees and the like are still controversial at present. There are studies showing that chronic low dose radiation can cause poor resistance, lassitude, and correlation between clinical symptoms of the irradiated and low dose radiation dose in humans or animals, such as 490 patients complaining of occupational clinical symptoms (neurasthenia, alopecia, bleeding tendency, hyposexuality, susceptibility to cold, etc.) in 1072 subjects in a study, in which 476 patients (80.41%) and 14 patients (2.9%) in the control group. The rate of positive clinical symptoms increases with increasing cumulative dose and time of irradiation, and is positively correlated, and the number of Red Blood Cells (RBC) at different cumulative doses is statistically significant (Wushaoxing, et al. investigation of the impact of long-term low-dose occupational irradiation on health of radiologists. J. toxicology, 2008,22(5):389 + 391). Thus in low dose radiation, the cumulative dose of different shots has a direct effect on the extent of the damage.
However, clinical symptoms of chronic low-dose radiation are mainly described by patient ambiguity, and it is difficult to exclude subjective assumption for accurate diagnosis, while clinical studies are mainly determined by the population proportion of corresponding clinical symptoms in large-scale test samples, and there is no more standard diagnosis for the cumulative dose of radiation to a patient and whether there are any symptoms of injury. Therefore, the prediction of the accumulated dose in the long-term low-dose radiation through the biological marker has great significance for the injury assessment and the consequence prediction of the person who is subjected to the long-term low-dose radiation.
Human studies in mice and rhesus monkeys have shown that detection of serum or plasma proteins such as Flt3L, SAA, IL-6, G-CSF, etc., can be used to assess the dose of irradiation to an animal early after irradiation, and is one of the biological dosimetry methods. However, plasma proteins are mainly used for prediction of moderate-heavy radiation dose and damage, and until now, no human has used the expression level of plasma proteins and cytokines for dose evaluation of low-dose irradiated persons and animals.
Prediction of medium and high dose radiation dose and extent of damage cannot be used for low dose radiation. The harmful effects of moderate and high doses of ionizing radiation on the body have been well defined, however, the exploration and discussion of the biological effects of low levels of radiation, despite 1 century, has now been largely elusive. The low dose radiation shows diversity in biological effects, and the effects of different radiation sources are obviously different, so that the direct deduction of the biological effects of the high dose radiation is difficult. The health hazards of low-dose radiation are mainly the risk of long-term carcinogenesis, while early effects may have different manifestations with different radiation quality, dose rate and different irradiated individuals, including adaptive response, low-dose radiation hypersensitivity and side effects (Zhou Ping Kun, low-dose radiation effect and revelation of radiation protection, 2004, Hai Kou, national medical radiation protection and safety academic seminars). Therefore, the existing medium-high dose radiation dose and damage prediction method cannot be applied to the dose and damage prediction of low-dose radiation.
Disclosure of Invention
The invention aims to provide application of a plasma protein combination in preparing a product for predicting low-dose radiation exposure dose.
In a first aspect, the invention claims the use of substance a in any one of:
(A1) preparing a product for predicting a low dose radiation exposure dose;
(A2) preparing a product for predicting the number and/or duration of low dose radiation exposures;
the substance A is a substance which can be used for detecting the content of IL-5, IL-12p40 and/or SELP in blood plasma. The substance A is preferably a substance which can be used for detecting the content of at least two or more of IL-5, IL-12p40 and SELP in plasma.
Wherein, the substance A can be a composition or a single substance. The single substance can detect the content of at least one of IL-5, IL-12p40 and SELP in plasma; the composition can be prepared by combining at least two of three substances which are respectively used for detecting the content of three proteins of IL-5, IL-12p40 and SELP in plasma.
In a second aspect, the invention claims the use of substance a and substance b in any one of:
(A1) preparing a product for predicting a low dose radiation exposure dose;
(A2) preparing a product for predicting the number and/or duration of low dose radiation exposures;
the substance A is a substance which can be used for detecting the content of IL-5, IL-12p40 and/or SELP in blood plasma; the substance B is a substance which can be used for detecting the content of IL-10 and/or SAA1 in blood plasma. The substance A is preferably a substance which can be used for detecting the content of at least two or more of IL-5, IL-12p40 and SELP in plasma.
Wherein, the substance A can be a composition or a single substance. The single substance can detect the content of at least one of IL-5, IL-12p40 and SELP in plasma; the composition can be prepared by combining at least two of three substances which are respectively used for detecting the content of three proteins of IL-5, IL-12p40 and SELP in plasma.
The substance B can be a composition or a single substance. The composition can be prepared by combining two substances which are respectively used for detecting the contents of two proteins of IL-10 and SAA1 in blood plasma.
In both aspects, the low-dose radiation exposure may be a long-term multiple low-dose radiation.
Further, in (a1), the predicted low-dose radiation exposure dose may be a cumulative exposure dose of the predicted long-term multiple times of low-dose radiation.
In a third aspect, the invention claims any of the following applications:
(I) use of substance A in the preparation of product A.
The substance A is a substance which can be used for detecting the content of IL-5, IL-12p40 and/or SELP in blood plasma. The substance A is preferably a substance which can be used for detecting the content of at least two or more of IL-5, IL-12p40 and SELP in plasma.
The product A can compare the accumulated irradiation dose of the long-term multiple low-dose radiation experienced by the animal A to be detected and the animal B to be detected on the premise of the same irradiation times and duration.
(II) application of substance C in preparation of product B.
The substance C is a substance which can be used for detecting the content of IL-5, IL-12p40, SELP and/or IL-10 in blood plasma. The substance C is preferably a substance which can be used for detecting the content of at least two or more of the four proteins of IL-5, IL-12p40, SELP and IL-10 in blood plasma.
The product B can compare the irradiation times and/or duration of the long-term multiple low-dose radiation experienced by the animal A to be detected and the animal B to be detected on the premise of the same total irradiation dose.
In (I) and (II), the test animal a and the test animal B are of the same species.
In (II), the substance C may be a composition or a single substance. The single substance can detect the content of at least one of IL-5, IL-12p40, SELP and IL-10 in plasma; the composition can be prepared by combining at least two of four substances which are respectively used for detecting the content of the four proteins of IL-5, IL-12p40, SELP and IL-10 in plasma.
(III) use of substance A or substance D in the preparation of product C;
the substance A is a substance which can be used for detecting the content of IL-5, IL-12p40 and/or SELP in blood plasma; the substance D consists of the substance A and a substance which can be used for detecting the content of SAA1 and/or IL-10 in blood plasma. The substance A is preferably a substance which can be used for detecting the content of at least two or more of IL-5, IL-12p40 and SELP in plasma.
The product C is capable of assessing whether the test animal has undergone multiple low dose radiation treatments over an extended period of time.
Wherein, the substance A can be a composition or a single substance. The single substance can detect the content of at least one of IL-5, IL-12p40 and SELP in plasma; the composition can be prepared by combining at least two of three substances which are respectively used for detecting the content of three proteins of IL-5, IL-12p40 and SELP in plasma.
In a fourth aspect, the invention claims any of the following data processing apparatus.
(I) A data processing apparatus a having the following functions:
on the premise of equal irradiation times and duration, comparing the accumulated irradiation dose of long-term multiple low-dose radiation experienced by the animal A to be detected and the animal B to be detected;
the animal A to be detected and the animal B to be detected are of the same species.
The data processing device a may include the following modules:
(a1) a data receiving module a; the data receiving module a is configured to receive IL-5, IL-12p40 and/or SELP (preferably more than two proteins) content values in the plasma of the test animal A and the test animal B;
(a2) a data comparison module a; the data comparison module a is configured to receive the content values of IL-5, IL-12p40 and/or SELP (preferably more than two proteins) in the plasma of the animal a to be tested and the animal B to be tested sent by the data reception module a, and compare the content values of the same protein in the plasma of the animal a to be tested and the animal B to be tested;
(a3) a judging module a; the judging module a is configured to receive the comparison result sent by the data comparing module a, and judge the comparison result according to a preset judging condition a, and the animal to be tested meeting the preset judging condition a "the accumulated irradiation dose of the long-term multiple low-dose radiation is relatively higher on the premise of the same irradiation times and duration".
The predetermined determination condition a may be: the plasma IL-5 and/or IL-12p40 content value is relatively high; and/or the amount of SELP content in plasma is relatively low.
(II) a data processing apparatus B having the following functions:
and comparing the irradiation times and/or duration of the low-dose radiation of the animal A to be tested and the animal B to be tested for multiple times in a long term on the premise of the same total irradiation dose.
The animal A to be detected and the animal B to be detected are of the same species.
The data processing device B may comprise the following modules:
(b1) a data receiving module b; the data receiving module B is configured to receive IL-5, IL-12p40, SELP and/or IL-10 (preferably more than two proteins) content values in the plasma of the test animal A and the test animal B;
(b2) a data comparison module b; the data comparison module B is configured to receive the content values of IL-5, IL-12p40, SELP and/or IL-10 (preferably more than two proteins) in the plasma of the animal a to be tested and the animal B to be tested sent by the data reception module B, and compare the content values of the same protein in the plasma of the animal a to be tested and the animal B to be tested;
(b3) a judging module b; the judging module b is configured to receive the comparison result sent by the data comparing module b, and judge the comparison result according to a preset judging condition b, and the animal to be tested meeting the preset judging condition b is less in the number of times of irradiation and/or duration of low-dose radiation for a long time on the premise that the total irradiation dose is the same.
The predetermined determination condition b may be: the plasma IL-5, IL-12p40 and/or IL-10 (preferably more than two proteins) content value is relatively high; and/or the amount of SELP content in plasma is relatively low.
(III) a data processing apparatus C having the following functions:
it is possible to assess whether the test animal has undergone multiple low-dose exposures over an extended period of time.
The data processing device C comprises the following modules:
(c1) a data receiving module c; the data receiving module c is configured to receive values of IL-5, IL-12p40, SELP, SAA1 and/or IL-10 (preferably more than two proteins) content in the plasma of the test animals and the control animals;
(c2) a data comparison module c; the data comparison module c is configured to receive the content values of IL-5, IL-12p40, SELP, SAA1 and/or IL-10 (preferably more than two proteins) in the blood plasma of the test animal and the control animal sent by the data reception module c, and compare the content values of the same protein in the blood plasma of the test animal and the control animal;
(c3) a judging module c; the judging module c is configured to receive the comparison result sent by the data comparing module c and judge the comparison result according to a preset judging condition c, and the animal to be tested meeting the preset judging condition c is subjected to long-term multiple low-dose radiation.
The control animal and the test animal are of the same species and are not irradiated.
The predetermined determination condition c may be: if the plasma IL-5, IL-12p40 and/or IL-10 (preferably more than two proteins) content of the animal to be tested is higher than that of the control animal; and/or, the amount of SAA1 and/or SELP in the plasma of the test animal is lower than that of the control animal, the test animal has undergone multiple low-dose radiation sessions over an extended period of time.
Wherein the animal to be tested can be a person suspected to have undergone multiple low-dose irradiations for a long time.
The data processing device a, the data processing device B, and the data processing device C may further include a control module or a controller, and the control module or the controller is configured to control each module.
In the present invention, the functions of the control module or controller are input of control data and output of results, transmission of data between modules, and data processing routines of the modules, and thus any control device or controller, such as a Central Processing Unit (CPU), a control chip for an industrial computer, etc., may be used as long as the above functions are achieved.
In a fifth aspect, the invention claims any of the following systems:
(I) system a having the following functions:
and on the premise of the same irradiation times and duration, comparing the accumulated irradiation dose of the long-term multiple low-dose radiation experienced by the animal A to be detected and the animal B to be detected.
The animal A to be detected and the animal B to be detected are of the same species;
the system a comprises a substance that can be used for detecting IL-5, IL-12p40 and/or SELP (preferably more than two proteins) content in plasma and a control device a configured or programmed to perform the following steps:
receiving values of IL-5, IL-12p40 and/or SELP (preferably more than two proteins) content in the plasma of said test animal A and said test animal B;
comparing the IL-5, IL-12p40 and/or SELP (preferably more than two proteins) content values in the plasma of the test animal A and the test animal B to obtain a comparison result;
and judging the comparison result according to a preset judgment condition a, wherein the animal to be detected meeting the preset judgment condition a is higher in accumulated irradiation dose of long-term multiple low-dose radiation on the premise of the same irradiation times and duration.
The predetermined determination condition a may be: the plasma IL-5 and/or IL-12p40 content value is relatively high; and/or the amount of SELP content in plasma is relatively low.
(II) System B having the following functions:
and comparing the irradiation times and/or duration of the low-dose radiation of the animal A to be tested and the animal B to be tested for multiple times in a long term on the premise of the same total irradiation dose.
The animal A to be detected and the animal B to be detected are of the same species.
The system B comprises a substance which can be used for detecting the IL-5, IL-12p40, SELP and/or IL-10 (preferably more than two proteins) content in plasma and a control device B which is configured or programmed to perform the following steps:
receiving values of IL-5, IL-12p40, SELP and/or IL-10 (preferably more than two proteins) content in the plasma of said test animal A and said test animal B;
comparing the IL-5, IL-12p40, SELP and/or IL-10 (preferably more than two proteins) content values in the blood plasma of the animal A and the animal B to obtain a comparison result;
and judging the comparison result according to a preset judgment condition b, wherein the animal to be tested meeting the preset judgment condition b is less in the irradiation times and/or duration of long-term multiple low-dose radiation on the premise of the same total irradiation dose.
The predetermined determination condition b may be: the plasma IL-5, IL-12p40 and/or IL-10 (preferably more than two proteins) content value is relatively high; and/or the amount of SELP content in plasma is relatively low.
(III) system C with the following specific functions:
it is possible to assess whether the test animal has undergone multiple low-dose exposures over an extended period of time.
The system C comprises a substance that can be used to detect the IL-5, IL-12p40, SELP, SAA1 and/or IL-10 (preferably more than two proteins) content in plasma and a control device C configured or programmed to perform the following steps:
receiving values of IL-5, IL-12p40, SELP, SAA1 and/or IL-10 (preferably more than two proteins) content in the plasma of the test animals and the control animals;
comparing the IL-5, IL-12p40, SELP, SAA1 and/or IL-10 (preferably more than two proteins) content values in the plasma of the test and control animals to obtain a comparison result;
and judging the comparison result according to a preset judgment condition c, wherein the animal to be detected meeting the preset judgment condition c is subjected to long-term multiple low-dose radiation.
The control animal and the test animal are of the same species and are not irradiated.
The predetermined determination condition c may be: if the plasma IL-5, IL-12p40 and/or IL-10 (preferably more than two proteins) content of the animal to be tested is higher than that of the control animal; and/or, the amount of SAA1 and/or SELP in the plasma of the test animal is lower than that of the control animal, the test animal has undergone multiple low-dose radiation sessions over an extended period of time.
Wherein the animal to be tested can be a person suspected to have undergone multiple low-dose irradiations for a long time.
In this aspect, the control device a, the control device B, and the control device C may each be any computer capable of executing the above-described steps, such as a general-purpose computer such as a Personal Computer (PC), an industrial control computer, or the like.
Further, the system may also include an input device and an output device; the input device is configured to input dynamically acquired data of a radioactivity count of the abdomen of the subject from the SPECT/CT instrument; the output device is configured to output the determination result.
In the present invention, the input device may be any type of input device commonly used for various types of data, for example, a keyboard, a mouse, a camera, a scanner, a light pen, a handwriting input board, a joystick, a voice input device, and the like. The output device may be any type of output device commonly used for various types of data, such as a display, a printer, a plotter, an image output system, a voice output system, a magnetic recording device, and so forth.
In a sixth aspect, the invention claims any one of the following computer-readable storage media.
(I) A computer-readable storage medium A;
the computer-readable storage medium a stores a computer program for executing the steps of:
(ii) IL-5, IL-12p40 and/or SELP (preferably more than two proteins) content values in the plasma of the test animal A and the test animal B that are of the same species and that both have undergone multiple low doses of radiation over an extended period of time;
comparing the IL-5, IL-12p40 and/or SELP (preferably more than two proteins) content values in the plasma of the test animal A and the test animal B to obtain a comparison result;
and judging the comparison result according to a preset judgment condition a, wherein the animal to be detected meeting the preset judgment condition a is higher in accumulated irradiation dose of long-term multiple low-dose radiation on the premise of the same irradiation times and duration.
The predetermined determination condition a may be: the plasma IL-5 and/or IL-12p40 content value is relatively high; and/or the amount of SELP content in plasma is relatively low.
(II) computer-readable storage medium B;
the computer-readable storage medium B stores a computer program for executing the steps of:
receiving values of IL-5, IL-12p40, SELP and/or IL-10 (preferably more than two proteins) content in plasma of said test animal A and said test animal B, both of which are of the same species and have undergone multiple low doses of radiation over an extended period of time;
comparing the IL-5, IL-12p40, SELP and/or IL-10 (preferably more than two proteins) content values in the blood plasma of the animal A and the animal B to obtain a comparison result;
and judging the comparison result according to a preset judgment condition b, wherein the animal to be tested meeting the preset judgment condition b is less in the irradiation times and/or duration of long-term multiple low-dose radiation on the premise of the same total irradiation dose.
The predetermined determination condition b may be: the plasma IL-5, IL-12p40 and/or IL-10 (preferably more than two proteins) content value is relatively high; and/or the amount of SELP content in plasma is relatively low.
(III) computer-readable storage medium C;
the computer-readable storage medium C stores a computer program for executing the steps of:
receiving values of IL-5, IL-12p40, SELP, SAA1 and/or IL-10 (preferably more than two proteins) content in plasma of said test animals and non-irradiated control animals of the same species and suspected of having undergone multiple low doses of radiation over an extended period of time;
comparing the IL-5, IL-12p40, SELP, SAA1 and/or IL-10 (preferably more than two proteins) content values in the plasma of the test and control animals to obtain a comparison result;
and judging the comparison result according to a preset judgment condition c, wherein the animal to be detected meeting the preset judgment condition c is subjected to long-term multiple low-dose radiation.
The predetermined determination condition c may be: if the plasma IL-5, IL-12p40 and/or IL-10 (preferably more than two proteins) content of the animal to be tested is higher than that of the control animal; and/or, the amount of SAA1 and/or SELP in the plasma of the test animal is lower than that of the control animal, the test animal has undergone multiple low-dose radiation sessions over an extended period of time.
In a seventh aspect, the invention claims any of the following methods:
the method I comprises the following steps: a method for comparing the cumulative irradiation dose height of a plurality of long-term low-dose radiations experienced by an animal A to be tested and an animal B to be tested on the premise of equal irradiation times and duration time comprises the following steps:
(d1) detecting the content values of IL-5, IL-12p40 and/or SELP (preferably more than two proteins) in the blood plasma of the animal A to be detected and the animal B to be detected;
(d2) comparing the content values of IL-5, IL-12p40 and/or SELP (preferably more than two proteins) in the blood plasma of the animal A to be tested and the animal B to be tested, and determining whether the cumulative irradiation dose of the animal A to be tested and the animal B to be tested subjected to long-term multiple low-dose radiation is relatively higher on the premise that the total irradiation dose is the same according to the following steps: "relatively high values of IL-5 and/or IL-12p40 (preferably more than two proteins) content in plasma; and/or, the animal to be tested having a relatively low value of SELP content in plasma is subjected to a relatively higher cumulative exposure dose of multiple long-term low-dose radiation given for the same exposure times and durations.
Method II: a method for comparing the number and/or duration of multiple low-dose exposures experienced by a test animal a and a test animal B over an extended period of time with the same total exposure dose, comprising the steps of:
(e1) detecting the content values of IL-5, IL-12p40, SELP and/or IL-10 (preferably more than two proteins) in the blood plasma of the animal A to be detected and the animal B to be detected;
(e2) comparing the content values of IL-5, IL-12p40, SELP and/or IL-10 (preferably more than two proteins) in the blood plasma of the animal A to be tested and the animal B to be tested, and determining whether the animal A to be tested or the animal B to be tested is subjected to relatively fewer irradiation times and/or durations of long-term multiple low-dose radiation on the premise that the total irradiation dose is the same according to the following steps: "relatively high values of IL-5, IL-12p40 and/or IL-10 (preferably more than two proteins) content in plasma; and/or, the test animal having a relatively low value of SELP content in plasma "has experienced fewer and/or fewer exposures of multiple low-dose radiation over an extended period of time, given the same total exposure dose.
In methods I and II, the test animal a and the test animal B are of the same species.
Method III: a method of assessing whether a test animal has undergone multiple low-dose exposures for an extended period of time, comprising the steps of:
(f1) detecting the content values of IL-5, IL-12p40, SELP, SAA1 and/or IL-10 (preferably more than two proteins) in the blood plasma of the animal to be detected and the control animal;
(f2) comparing the values of IL-5, IL-12p40, SELP, SAA1 and/or IL-10 (preferably more than two proteins) content in the plasma of the test and control animals, determining whether the test animal has undergone multiple low dose irradiation for an extended period of time as follows: if the plasma IL-5, IL-12p40 and/or IL-10 (preferably more than two proteins) content of the animal to be tested is higher than that of the control animal; and/or, the amount of SAA1 and/or SELP in the plasma of the test animal is lower than that of the control animal, the test animal has undergone multiple low-dose radiation sessions over an extended period of time.
The control animal and the test animal are of the same species and are not irradiated.
Wherein the animal to be tested can be a person suspected to have undergone multiple low-dose irradiations for a long time.
In the method III, preferably, at least two of IL-5, IL-12p40 and SELP have different expressions; preferably there is a difference in SAA 1; there may or may not be a difference in IL-10.
In this aspect, the method is a non-disease diagnostic therapeutic method.
In the above aspects, the irradiation dose of the single low-dose radiation of the long-term plurality of times of low-dose radiation may be 0.02 to 0.5 Gy.
In the above aspects, the long term multiple times may be: one or more times per week.
Further, the long-term number of times may be: five or more weeks, once or twice or more weekly.
In the above aspects, the substance for detecting the content of IL-5, IL-12p40, SELP, IL-10 and/or SAA1 (preferably two or more proteins) in plasma may be a substance capable of specifically binding to the corresponding protein, such as an antibody or an ELISA kit containing the antibody, or the like.
In each of the above aspects, the test animal may be a mammal.
Further, the mammal may be a human or a mouse.
In a particular embodiment of the invention, the mammal is in particular a mouse.
In a particular embodiment of the invention, the radiation is in particular gamma-rays (in particular as60Co gamma-rays).
The invention uses antibody chip technology to carry out preliminary detection on the levels of various proteins and cytokines in plasma of a mouse after long-term continuous low-dose radiation, simultaneously uses an ELISA method to detect the influence of low-dose radiation dose and radiation frequency (and duration) on plasma protein expression, finds that the expression of various protein molecules such as IL-5, IL-12P40, SELP and the like in the plasma is related to the dose of the low-dose radiation, and the expression difference has significant significance (P <0.05), and also finds that the levels of the plasma protein molecules are related to the radiation frequency and the duration or the concentration degree (P < 0.05). In addition, IL-10 also had similar effects, but only significantly different at the higher dose (0.5Gy) or single exposure, and corresponding dose-effect relationships (although P-values were not significant) at other doses or other exposure times, and in addition, the plasma SAA1 levels were associated with low dose radiation exposure doses, but not with exposure times and durations. Therefore, IL-10, SAA1 and the like can be used as auxiliary detection indexes to assist IL-5, IL-12p40 and SELP in judging the total irradiation dose of low-dose radiation, and the expression of plasma MMP14 has no significant relation with each dose of the low-dose radiation, so that the MMP is not suitable for being used as a marker of the low-dose radiation.
The invention finds that the plasma protein combination can be used as an index for predicting long-term low-dose radiation accumulated dose, and further provides the application of the plasma protein combination in predicting the long-term low-dose radiation accumulated dose. The application is of great significance in diagnosing cumulative radiation dose to a radiologist threatened by long-term low-dose radiation.
Drawings
FIG. 1 shows the results of analysis of plasma protein signal intensity versus thermogram analysis of the antibody chip after each group irradiation.
Fig. 2 is a comparison result of signal intensity of proteins with significant differences screened after irradiation of each group in the antibody chip analysis result. P <0.1, P <0.05, P < 0.01.
FIG. 3 is a graph showing the results of plasma IL-5 expression in mice after low-dose irradiation, which was confirmed by ELISA assay. P <0.05, P < 0.001.
Left panel: after the same multiple (10) low dose exposures, the level of mouse plasma IL-5 increased with increasing total exposure dose, with statistical differences between groups; right panel: the level of IL-5 in plasma of mice after a single dose of 0.5Gy irradiation was significantly higher than when irradiated in multiple fractions (5 and 10) at the same dose, with statistical differences. The result shows that the mouse plasma IL-5 can be used as a biomarker molecule for predicting the low-dose radiation dose and the radiation irradiation frequency/duration, and the higher the irradiation dose is, the higher the plasma IL-5 expression is on the premise of the same irradiation frequency and duration; the fewer the number and duration of irradiation, the higher the plasma IL-5 expression at the same irradiation dose.
FIG. 4 is a graph showing the results of plasma IL-10 expression in mice after low-dose irradiation, which was confirmed by ELISA assay. P < 0.05.
Left panel: after the same multiple (10) low dose exposures, the level of mouse plasma IL-10 increased with increasing total exposure dose, but only the 0.05Gy × 10 exposure group had a significant difference (P <0.05) compared to the control group, while the 0.05Gy × 10 exposure group had no statistical difference from the 0.02Gy × 10 exposure group; right panel: the level of mouse plasma IL-5 after a single dose of 0.5Gy irradiation was significantly higher than when irradiated in multiple fractions (5 and 10) at the same dose (P < 0.05). The result shows that the mouse plasma IL-10 can be used as a biomarker molecule for assisting in predicting the low-dose radiation dose, but is not suitable for independently predicting the low-dose radiation dose, and on the premise of equal irradiation times and duration, when the irradiation dose exceeds a certain dose, the higher the irradiation dose is, the higher the IL-10 expression is; the fewer the number and duration of irradiation, the higher the expression of IL-10 at the same irradiation dose.
FIG. 5 is a graph showing the results of ELISA assay to verify the expression of plasma IL-12p40 after low-dose irradiation in mice. P <0.05, P < 0.01.
Left panel: after the same multiple (10) low dose exposures, the level of mouse plasma IL-12p40 increased with increasing total exposure dose, with statistical differences between groups; right panel: the level of mouse plasma IL-12P40 after a single dose of 0.5Gy irradiation was significantly higher than when irradiated multiple times (5 and 10 times) at the same dose (P < 0.05). The result shows that the mouse plasma IL-12p40 can be used as a biomarker molecule for predicting low-dose radiation dosage, and the higher the radiation dosage is, the higher the expression of the plasma IL-12p40 is on the premise of the same irradiation times and duration; the fewer the number and duration of irradiation, the higher the expression of plasma IL-12p40 at the same irradiation dose.
Figure 6 is a graph demonstrating the plasma MMP14 expression following low dose irradiation in mice by ELISA assay.
Left panel: after the same multiple (10) low dose irradiation, the level of mouse plasma MMP14 increased with increasing total irradiation dose, but there were no statistical differences between the groups; right panel: the level of mouse plasma MMP14 after a single dose of 0.5Gy irradiation was not statistically different between groups, although it was higher than when irradiated in multiple fractions (5 and 10) at the same dose. The results indicate that mouse plasma MMP14 may not be a biomarker molecule for predicting low dose radiation exposure doses.
FIG. 7 is a graph showing the results of plasma SAA1 expression in mice after low dose irradiation, which was confirmed by ELISA assay. P < 0.05.
Left panel: after the same multiple (10) low dose exposures, the level of mouse plasma SAA1 decreased with increasing total exposure dose, with statistical differences between each group compared to the control group, whereas the 0.05Gy × 10 exposure group was not statistically different from the 0.02Gy × 10 exposure group; right panel: the level of mouse plasma SAA1 after a single dose of 0.5Gy irradiation was not different from the level when irradiated multiple times (5 and 10 times) at the same dose. The results show that mouse plasma SAA1 can be used as a biomarker molecule for predicting low dose radiation exposure dose, and plasma SAA1 expression is increased after low dose irradiation, regardless of total irradiation dose.
FIG. 8 is a graph of plasma SELP expression results after low dose irradiation of mice, as verified by ELISA assay. P <0.05, P < 0.001.
Left panel: after the same number of (10) low dose exposures, the level of plasma SELP in mice decreased with increasing total exposure dose, with statistical differences in each group; right panel: the level of mouse plasma SELP after a single dose of 0.5Gy irradiation is significantly higher than when irradiated in multiple fractions (5 and 10) at the same dose (P < 0.05). The result shows that the mouse plasma SELP can be used as a biomarker molecule for predicting the low-dose radiation dose, and the higher the radiation dose is, the higher the plasma SELP expression is on the premise of the same irradiation times and duration; the fewer the number and duration of irradiation, the higher the plasma SELP expression at the same irradiation dose.
Detailed Description
The present invention is described in further detail below with reference to specific embodiments, which are given for the purpose of illustration only and are not intended to limit the scope of the invention. The examples provided below serve as a guide for further modifications by a person skilled in the art and do not constitute a limitation of the invention in any way.
The experimental procedures in the following examples, unless otherwise indicated, are conventional and are carried out according to the techniques or conditions described in the literature in the field or according to the instructions of the products. Materials, reagents and the like used in the following examples are commercially available unless otherwise specified.
Example 1 detection of plasma protein content Change on an antibody chip after Long-term multiple Low-dose irradiation
C57BL/6 mice: from Beijing Wittiulihua laboratory animal technology Co., Ltd, male, the weight is 18-22 g.
12C 57BL/6 mice, grouped and performed according to Table 160Co gamma-ray irradiation (military medical institute radiated medical research institute cobalt source, military scientific institute). All mice were bled via the heart 24 hours after the last irradiation and plasma was extracted. 3 mice were taken from each group, and analyzed and detected by using an antibody chip technique (Raybiotech, USA, Cat: AAM-BLG-1) according to the chip instructions.
TABLE 1 mouse irradiation protocol for mouse Low dose irradiation protein chip detection experiments
Figure BDA0002732731780000121
The results of analysis of plasma protein signal intensity versus thermograph of the antibody chip after irradiation of each group are shown in fig. 1, and the results show that the differences in protein expression levels between groups and between samples in each group are large, suggesting that the individual differences in plasma protein expression levels are large.
Through comparative screening, it is found that in the antibody chip experiment result, the expression of partial plasma proteins is significantly different between the low-dose irradiated group and the normal control group, such as IL-5, IL-10, IL-12p40, MMP14, SAA1 and SELP (FIG. 2).
Example 2 ELISA detection of plasma protein content Change after Long-term multiple Low-dose irradiation
According to the results of example 1, IL-5, IL-10, IL-12p40, MMP14, SAA1 and SELP were selected as the test subjects, and the content change of these proteins in plasma after long-term multiple low-dose irradiation was measured by using an ELISA kit.
40C 57BL/6 mice, grouped and performed according to Table 260Co gamma-ray irradiation. All mice were bled via the heart 24 hours after the last irradiation and plasma was extracted. Each group of 8 mice was tested for the expression levels of IL-5, IL-10, IL-12p40, MMP14, SAA1 and SELP in plasma using an ELISA kit. ELISA kit source (Elabscience, Wuhan, Inc.), detection was performed according to the ELISA kit instructions。
TABLE 2 mouse irradiation protocol for ELISA detection of plasma proteins after low dose irradiation in mice
Figure BDA0002732731780000122
Figure BDA0002732731780000131
The results show that:
1. after the same multiple (10) low dose exposures, the level of mouse plasma IL-5 increased with increasing total exposure dose, with statistical differences between groups. The level of IL-5 in plasma of mice after a single dose of 0.5Gy irradiation was significantly higher than when irradiated in multiple fractions (5 and 10) at the same dose, with statistical differences. The result shows that the mouse plasma IL-5 can be used as a biomarker molecule for predicting the low-dose radiation dose and the radiation irradiation frequency/duration, and the higher the irradiation dose is, the higher the plasma IL-5 expression is on the premise of the same irradiation frequency and duration; the fewer the number and duration of irradiation, the higher the plasma IL-5 expression at the same irradiation dose.
2. After the same number of low dose exposures (10), the level of mouse plasma IL-10 increased with increasing total exposure dose, but only the 0.05Gy × 10 exposure group had a significant difference (P <0.05) compared to the control group, whereas the 0.05Gy × 10 exposure group had no statistical difference from the 0.02Gy × 10 exposure group. The level of mouse plasma IL-5 after a single dose of 0.5Gy irradiation was significantly higher than when irradiated in multiple fractions (5 and 10) at the same dose (P < 0.05). The result shows that the mouse plasma IL-10 can be used as a biomarker molecule for assisting in predicting the low-dose radiation dose, but is not suitable for independently predicting the low-dose radiation dose, and on the premise of equal irradiation times and duration, when the irradiation dose exceeds a certain dose, the higher the irradiation dose is, the higher the IL-10 expression is; the fewer the number and duration of irradiation, the higher the expression of IL-10 at the same irradiation dose.
3. After the same multiple (10) low dose exposures, the level of mouse plasma IL-12p40 increased with increasing total exposure dose, with statistical differences between groups. The level of mouse plasma IL-12P40 after a single dose of 0.5Gy irradiation was significantly higher than when irradiated multiple times (5 and 10 times) at the same dose (P < 0.05). The result shows that the mouse plasma IL-12p40 can be used as a biomarker molecule for predicting low-dose radiation dosage, and the higher the radiation dosage is, the higher the expression of the plasma IL-12p40 is on the premise of the same irradiation times and duration; the fewer the number and duration of irradiation, the higher the expression of plasma IL-12p40 at the same irradiation dose.
4. After the same multiple (10) low dose irradiation, the level of mouse plasma MMP14 increased with increasing total irradiation dose, but there was no statistical difference between the groups. The level of mouse plasma MMP14 after a single dose of 0.5Gy irradiation was not statistically different between groups, although it was higher than when irradiated in multiple fractions (5 and 10) at the same dose. The results indicate that mouse plasma MMP14 may not be a biomarker molecule for predicting low dose radiation exposure doses.
5. After the same multiple (10) low dose exposures, the level of mouse plasma SAA1 decreased with increasing total exposure dose, with statistical differences between each group compared to the control group, whereas the 0.05Gy × 10 exposure group was not statistically different from the 0.02Gy × 10 exposure group. The level of mouse plasma SAA1 after a single dose of 0.5Gy irradiation was not different from the level when irradiated multiple times (5 and 10 times) at the same dose. The results indicate that mouse plasma SAA1 can be used as a biomarker molecule for predicting low dose radiation exposure dose, and that plasma SAA1 expression is reduced after low dose exposure, regardless of total exposure dose.
6. After the same multiple (10) low dose exposures, the level of plasma SELP in mice decreased with increasing total exposure dose, with statistical differences between groups. The level of mouse plasma SELP after a single dose of 0.5Gy irradiation is significantly higher than when irradiated in multiple fractions (5 and 10) at the same dose (P < 0.05). The result shows that the mouse plasma SELP can be used as a biomarker molecule for predicting the low-dose radiation dose, and the higher the radiation dose is, the lower the plasma SELP expression is on the premise of the same irradiation times and duration; the fewer the number and duration of irradiation, the lower the plasma SELP expression at the same irradiation dose.
The present invention has been described in detail above. It will be apparent to those skilled in the art that the invention can be practiced in a wide range of equivalent parameters, concentrations, and conditions without departing from the spirit and scope of the invention and without undue experimentation. While the invention has been described with reference to specific embodiments, it will be appreciated that the invention can be further modified. In general, this application is intended to cover any variations, uses, or adaptations of the invention following, in general, the principles of the invention and including such departures from the present disclosure as come within known or customary practice within the art to which the invention pertains. The use of some of the essential features is possible within the scope of the claims attached below.

Claims (10)

1. Use of substance a in any one of:
(A1) preparing a product for predicting a low dose radiation exposure dose;
(A2) preparing a product for predicting the number and/or duration of low dose radiation exposures;
the substance A is a substance which can be used for detecting the content of IL-5, IL-12p40 and/or SELP in blood plasma.
2. Use of substance a and substance b in any one of:
(A1) preparing a product for predicting a low dose radiation exposure dose;
(A2) preparing a product for predicting the number and/or duration of low dose radiation exposures;
the substance A is a substance which can be used for detecting the content of IL-5, IL-12p40 and/or SELP in blood plasma; the substance B is a substance which can be used for detecting the content of IL-10 and/or SAA1 in blood plasma.
3. Use according to claim 1 or 2, characterized in that: the low-dose radiation exposure is long-term multiple low-dose radiation.
4. Use according to claim 3, characterized in that: in (a1), the predicted low-dose radiation exposure dose is a cumulative exposure dose of the predicted long-term multiple times low-dose radiation.
5. Any of the following applications:
(I) the use of substance A in the preparation of product A;
the substance A is a substance which can be used for detecting the content of IL-5, IL-12p40 and/or SELP in blood plasma;
the product A can compare the accumulated irradiation dose of the long-term multiple low-dose radiation experienced by the animal A to be detected and the animal B to be detected on the premise of the same irradiation times and duration;
(II) use of substance C in the preparation of product B;
the substance C is a substance which can be used for detecting the content of IL-5, IL-12p40, SELP and/or IL-10 in blood plasma;
the product B can compare the irradiation times and/or duration of the long-term multiple low-dose radiation experienced by the animal A to be detected and the animal B to be detected on the premise of the same total irradiation dose;
the animal A to be detected and the animal B to be detected are of the same species;
(III) use of substance A or substance D in the preparation of product C;
the substance A is a substance which can be used for detecting the content of IL-5, IL-12p40 and/or SELP in blood plasma; the substance D consists of the substance A and a substance which can be used for detecting the content of SAA1 and/or IL-10 in blood plasma;
the product C is capable of assessing whether the test animal has undergone multiple low dose radiation treatments over an extended period of time.
6. Any one of the following data processing apparatuses:
a data processing device A; the data processing device A can compare the accumulated irradiation dose of the long-term multiple low-dose radiation experienced by the animal A to be detected and the animal B to be detected on the premise of equal irradiation times and duration;
the data processing device A comprises the following modules:
(a1) a data receiving module a; the data receiving module a is configured to receive IL-5, IL-12p40 and/or SELP content values in the plasma of the test animal A and the test animal B;
(a2) a data comparison module a; the data comparison module a is configured to receive the IL-5, IL-12p40 and/or SELP content values in the blood plasma of the animal A to be tested and the animal B to be tested sent by the data reception module a, and compare the content values of the same protein in the blood plasma of the animal A to be tested and the animal B to be tested;
(a3) a judging module a; the judging module a is configured to receive the comparison result sent by the data comparing module a, and judge the comparison result according to a preset judging condition a, and the animal to be tested meeting the preset judging condition a is higher in accumulated irradiation dose of long-term multiple low-dose radiation on the premise of equal irradiation times and duration;
a data processing device B; the data processing device B can compare the irradiation times and/or duration of the long-term multiple low-dose radiation experienced by the animal A to be detected and the animal B to be detected on the premise of the same total irradiation dose;
the data processing device B comprises the following modules:
(b1) a data receiving module b; the data receiving module B is configured to receive IL-5, IL-12p40, SELP and/or IL-10 content values in the plasma of the test animal A and the test animal B;
(b2) a data comparison module b; the data comparison module B is configured to receive the IL-5, IL-12p40, SELP and/or IL-10 content values in the plasma of the animal a to be tested and the animal B to be tested sent by the data reception module B, and compare the content values of the same protein in the plasma of the animal a to be tested and the animal B to be tested;
(b3) a judging module b; the judging module b is configured to receive the comparison result sent by the data comparing module b, and judge the comparison result according to a preset judging condition b, and the to-be-tested animal meeting the preset judging condition b is less in irradiation times and/or duration of long-term multiple low-dose radiation on the premise that the total irradiation dose is the same;
the animal A to be detected and the animal B to be detected are of the same species;
a data processing device C; the data processing device C can evaluate whether the animal to be tested is subjected to multiple low-dose radiation for a long time;
the data processing device C comprises the following modules:
(c1) a data receiving module c; the data receiving module c is configured to receive values of IL-5, IL-12p40, SELP, SAA1 and/or IL-10 content in the plasma of the test animals and control animals;
(c2) a data comparison module c; the data comparison module c is configured to receive the IL-5, IL-12p40, SELP, SAA1 and/or IL-10 content values in the blood plasma of the test animal and the control animal sent by the data reception module c, and compare the content values of the same protein in the blood plasma of the test animal and the control animal;
(c3) a judging module c; the judging module c is configured to receive the comparison result sent by the data comparing module c and judge the comparison result according to a preset judging condition c, and the animal to be tested meeting the preset judging condition c is subjected to long-term multiple low-dose radiation;
the control animal and the test animal are of the same species and are not irradiated.
7. Any one of the following systems:
a system A; the system A can compare the accumulated irradiation dose of the long-term multiple low-dose radiation experienced by the animal A to be detected and the animal B to be detected on the premise of the same irradiation times and duration; the animal A to be detected and the animal B to be detected are of the same species;
the system a comprises a substance that can be used for detecting IL-5, IL-12p40 and/or SELP levels in plasma and a control device a configured or programmed to perform the following steps:
receiving IL-5, IL-12p40 and/or SELP content values in the plasma of the test animal A and the test animal B;
comparing the IL-5, IL-12p40 and/or SELP content values in the plasma of the test animal A and the test animal B to obtain a comparison result;
judging a comparison result according to a preset judgment condition a, wherein the animal to be detected meeting the preset judgment condition a is higher in accumulated irradiation dose of long-term multiple low-dose radiation on the premise of equal irradiation times and duration;
a system B; the system B can compare the irradiation times and/or duration of the long-term multiple low-dose radiation experienced by the animal A to be detected and the animal B to be detected on the premise of the same total irradiation dose; the animal A to be detected and the animal B to be detected are of the same species;
the system B comprises a substance which can be used for detecting IL-5, IL-12p40, SELP and/or IL-10 levels in plasma and a control device B which is configured or programmed to carry out the following steps:
receiving IL-5, IL-12p40, SELP and/or IL-10 content values in the plasma of the test animal A and the test animal B;
comparing the IL-5, IL-12p40, SELP and/or IL-10 content values in the plasma of the test animal A and the test animal B to obtain a comparison result;
judging a comparison result according to a preset judgment condition b, wherein the animal to be detected meeting the preset judgment condition b is less in irradiation times and/or duration of long-term multiple low-dose radiation on the premise that the total irradiation dose is the same;
a system C; the system C can evaluate whether the animal to be tested has undergone multiple low-dose radiation for a long time;
the system C comprises a substance which can be used for detecting the IL-5, IL-12p40, SELP, SAA1 and/or IL-10 content in plasma and a control device C which is configured or programmed to carry out the following steps:
receiving values of IL-5, IL-12p40, SELP, SAA1 and/or IL-10 content in plasma of the test animals and the control animals;
comparing the IL-5, IL-12p40, SELP, SAA1 and/or IL-10 content values in the plasma of the test animal and the control animal to obtain a comparison result;
judging a comparison result according to a preset judgment condition c, wherein the animal to be detected meeting the preset judgment condition c is subjected to long-term multiple low-dose radiation;
the control animal and the test animal are of the same species and are not irradiated.
8. Any one of the following computer-readable storage media:
a computer-readable storage medium A; the computer-readable storage medium a stores a computer program for executing the steps of:
receiving values of IL-5, IL-12p40 and/or SELP content in plasma of said test animal A and said test animal B that are of the same species and both have undergone multiple low doses of radiation over an extended period of time;
comparing the IL-5, IL-12p40 and/or SELP content values in the plasma of the test animal A and the test animal B to obtain a comparison result;
judging a comparison result according to a preset judgment condition a, wherein the animal to be detected meeting the preset judgment condition a is higher in accumulated irradiation dose of long-term multiple low-dose radiation on the premise of equal irradiation times and duration;
a computer-readable storage medium B; the computer-readable storage medium B stores a computer program for executing the steps of:
receiving values of IL-5, IL-12p40, SELP and/or IL-10 content in plasma of said test animal A and said test animal B that are of the same species and both have undergone multiple low doses of radiation over an extended period of time;
comparing the IL-5, IL-12p40, SELP and/or IL-10 content values in the plasma of the test animal A and the test animal B to obtain a comparison result;
judging a comparison result according to a preset judgment condition b, wherein the animal to be detected meeting the preset judgment condition b is less in irradiation times and/or duration of long-term multiple low-dose radiation on the premise that the total irradiation dose is the same;
a computer-readable storage medium C; the computer-readable storage medium C stores a computer program for executing the steps of:
receiving values of IL-5, IL-12p40, SELP, SAA1, and/or IL-10 content in plasma of the test animal and non-irradiated control animals that are of the same species and are suspected of having undergone multiple low doses of radiation over an extended period of time;
comparing the IL-5, IL-12p40, SELP, SAA1 and/or IL-10 content values in the plasma of the test animal and the control animal to obtain a comparison result;
and judging the comparison result according to a preset judgment condition c, wherein the animal to be detected meeting the preset judgment condition c is subjected to long-term multiple low-dose radiation.
9. Any one of the following methods:
the method I comprises the following steps: a method for comparing the accumulated irradiation dose height of a plurality of long-term low-dose radiations experienced by an animal A to be tested and an animal B to be tested on the premise of equal irradiation times and duration time comprises the following steps:
(d1) detecting IL-5, IL-12p40 and/or SELP content values in the blood plasma of the animal A to be detected and the animal B to be detected;
(d2) comparing the content values of IL-5, IL-12p40 and/or SELP in the blood plasma of the animal A to be tested and the animal B to be tested, and determining whether the cumulative irradiation dose of the animal A to be tested or the animal B to be tested subjected to long-term multiple low-dose radiation is relatively higher on the premise that the total irradiation dose is the same according to the following steps: "relatively high values of IL-5 and/or IL-12p40 content in plasma; and/or, the accumulated irradiation dose of multiple low-dose radiation for a long time is relatively higher for the animal to be tested with relatively low SELP content value in plasma under the premise of the same irradiation times and duration;
method II: a method for comparing the irradiation times and/or duration of multiple low-dose radiation for a long time of an animal A to be tested and an animal B to be tested on the premise of the same total irradiation dose comprises the following steps:
(e1) detecting the content values of IL-5, IL-12p40, SELP and/or IL-10 in the blood plasma of the animal A to be detected and the animal B to be detected;
(e2) comparing the content values of IL-5, IL-12p40, SELP and/or IL-10 in the blood plasma of the animal A to be tested and the animal B to be tested, and determining whether the animal A to be tested or the animal B to be tested is subjected to relatively fewer irradiation times and/or durations of long-term multiple low-dose radiation on the premise that the total irradiation dose is the same according to the following steps: "relatively high values of IL-5, IL-12p40 and/or IL-10 content in plasma; and/or, the animal to be tested having a relatively low value of SELP content in plasma "has experienced fewer irradiation times and/or durations of multiple low-dose radiation for a long time on the premise that the total irradiation dose is the same";
the animal A to be detected and the animal B to be detected are of the same species;
method III: a method of assessing whether a test animal has undergone multiple low-dose exposures for an extended period of time, comprising the steps of:
(f1) detecting the content values of IL-5, IL-12p40, SELP, SAA1 and/or IL-10 in the blood plasma of the animal to be detected and the control animal;
(f2) comparing the values of IL-5, IL-12p40, SELP, SAA1 and/or IL-10 content in the plasma of the test and control animals to determine whether the test animal has undergone multiple low dose irradiation for an extended period of time as follows: if the plasma IL-5, IL-12p40 and/or IL-10 content value of the animal to be tested is higher than that of the control animal; and/or, the amount of SAA1 and/or SELP in the plasma of the test animal is lower than that of the control animal, the test animal has undergone multiple low-dose radiation for a long period of time;
the control animal and the test animal are of the same species and are not irradiated.
10. The application of any of claims 3-5 or the data processing apparatus of claim 6 or the system of claim 7 or the computer-readable storage medium of claim 8 or the method of claim 9, wherein: the irradiation dose of single low-dose radiation in the long-term multiple low-dose radiation is 0.02-0.5 Gy;
and/or
The long-term multiple times are: one or more than one week, once or more than one time per week;
further, the long-term times are: five or more weeks, once or twice or more weekly;
and/or
The radiation is gamma irradiation.
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