CN111060697A - Small intestine radioactive injury marking method using HMGB1 - Google Patents
Small intestine radioactive injury marking method using HMGB1 Download PDFInfo
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- CN111060697A CN111060697A CN201911389372.7A CN201911389372A CN111060697A CN 111060697 A CN111060697 A CN 111060697A CN 201911389372 A CN201911389372 A CN 201911389372A CN 111060697 A CN111060697 A CN 111060697A
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- 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
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- 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
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Abstract
The invention provides a small intestine radioactive injury marking method using HMGB1, which is characterized in that HMGB1 is used for translocating in nucleus and cytoplasm of small intestine mucosa, HMGB1 is released in small intestine fluid and peripheral blood, and HMGB1 content in feces is increased to mark small intestine radioactive injury. The injury marker is an essential tool for researching a medicament for preventing and treating the radioactive small intestine injury. The discovery that HMGB1 is used as a radioactive small intestine injury marker can effectively accelerate the screening of radioactive small intestine injury prevention and treatment drugs and further improve the evaluation system of the radioactive small intestine injury prevention and treatment drugs.
Description
Technical Field
The invention belongs to the technical field of medical detection, and particularly relates to a small intestine radioactive injury marking method using HMGB 1.
Background
The radiation can cause the change of vascular endothelial cells, mucosal epithelial cells, crypt stem cells, intestinal flora and the like in the intestinal tract, and is mainly manifested as the pathological changes of vascular swelling, occlusion, rupture or reduction in intestinal villus, intestinal villus shortening, lodging, intestinal wall fibrosis and the like. A plurality of researches are carried out on the pathogenesis of the radioactive intestinal injury at home and abroad, and the ionizing radiation is considered to cause the radioactive intestinal injury by influencing the structure and the function of biological target molecules, and mainly relates to complex mechanisms such as DNA (deoxyribonucleic acid) injury, structural and modification change of proteins, excessive release of inflammatory factors, uncontrolled signal conduction and the like.
High mobility histone 1(HMGB1) is closely associated with inflammatory responses. Under normal conditions, HMGB1 has cell nucleus tropism, mainly exists in cell nucleus, is a non-histone chromosome binding protein, participates in DNA recombination, repair, gene transcription control, cell replication, differentiation, maturation and other life activities, and only a very small amount of HMGB1 in cytoplasm and extracellular fluid can automatically return to the cell nucleus; however, when the body and cells are exogenously stimulated, HMGB1 loses nuclear tropism, translocates to the cytoplasm, and is secreted in large amounts into the extracellular fluid. Tracey and Lotze noted on NatureView Immunology: extracellular free HMGB1 is an important cause and indicator of the promotion of inflammatory responses. They can be used as the promoter of inflammatory reaction to induce the over-expression of downstream inflammatory factors IL-6, IL-8, etc.; the polypeptide is also an inflammatory factor, can act on vascular endothelial cells, up-regulates the expression of ICAM-1 and VCAM-1, and is combined with Toll-like protein receptors (TLRs) on cell membranes and the like, so that the TLR2-NF kappa B signal pathway conduction is unbalanced, and the inflammatory reaction is further aggravated.
Disclosure of Invention
The invention aims to provide a small intestine radioactive damage marking method by using HMGB1, which is used for marking small intestine radioactive damage by using HMGB1 translocation in nucleus and cytoplasm of small intestine mucosa and HMGB1 release in small intestine liquid and peripheral blood; specifically, the method is characterized in that the relative expression quantity of HMGB1 in the cell nucleus of the small intestine mucosal cell is detected, and 2-16Gy X-ray irradiation reduces the relative expression quantity of HMGB1 in the cell nucleus by more than half, translocates to cytoplasm and secretes into extracellular fluid; detecting the content of HMGB1 in serum, wherein the content of HMGB1 in the serum of a patient with small intestine radioactive injury is increased compared with that of a normal patient, and 2-16Gy X-ray irradiation increases the content of HMGB1 in the serum by 501.7-2315.3pg/ml, and the content is increased by 1.7-3.4 times; detecting the content of HMGB1 in small intestine fluid, wherein the content of HMGB1 in the small intestine fluid of a patient with radioactive small intestine injury is increased compared with that of a normal patient, and the content of HMGB1 in the small intestine fluid is increased by 28.4-177.0pg/ml and increased by 1.4-4.0 times by virtue of 2-16Gy X-ray irradiation; the content of the inflammatory factor IL-6 in the serum is detected, the content of the IL-6 in the serum of a patient with small intestine radioactive injury is increased compared with that of a normal patient, and the content of HMGB1 is increased by 1.1-5.9pg/ml and increased by 2.7-10.1 times by the 2-16Gy X-ray irradiation. The method detects the content of HMGB1 in the excrement, and the content of HMGB1 in the excrement is improved by more than 2 times and is more than 10 mu g/g.
Drawings
Figure 1. change in HMGB1 content in mice intestinal fluid after X-ray peritoneal irradiation (P <0.05 compared to the 0Gy group).
FIG. 2 shows the distribution and relative expression of HMGB1 in mouse intestinal villus cells after X-ray intraperitoneal irradiation.
Figure 3. change in HMGB1 content in mouse serum after X-ray intraperitoneal irradiation (P <0.05 compared to 0Gy group).
Figure 4. change in IL-6 content in mouse serum after X-ray intraperitoneal irradiation (P <0.05 compared to 0Gy group).
Figure 5. change in HMGB1 content in mouse feces after X-ray intraperitoneal irradiation (P <0.05 compared to the 0Gy group).
Detailed Description
The injury marker is an essential tool for researching a medicament for preventing and treating the radioactive small intestine injury. The discovery that HMGB1 is used as a radioactive small intestine injury marker can effectively accelerate the screening of radioactive small intestine injury prevention and treatment drugs and further improve the evaluation system of the radioactive small intestine injury prevention and treatment drugs.
The invention discloses a method for marking small intestine radioactive injury by utilizing translocation of HMGB1 in nucleus and cytoplasm of small intestine mucosa, release of HMGB1 in small intestine fluid and peripheral blood and content change of HMGB1 in feces, which is found for the first time, and HMGB1 can further induce release of inflammatory factor IL-6 to aggravate small intestine radiation injury. Changes in HMGB1 in mouse experiments may reflect to some extent changes in HMGB1 protein in human intestinal fluid and peripheral blood. Therefore, the mouse small intestine radioactive injury marking method using HMGB1 can be used for screening corresponding radioactive intestine injury prevention and treatment drugs and evaluating and researching drug effects.
Example 1 Change in Small intestine injury in mice by different ionizing radiation doses of HMGB1
The Balb/c mice are fed for 1 day after entering an animal room, grouped after the weight is stable, fed for 3 days adaptively, anesthetized by injecting sodium pentobarbital into the abdominal cavity, marked with picric acid, placed in a transparent independent fixing box after the lower edges of the xiphoid and ribs reach the abdominal cavity irradiation target area of thighbone, and placed on a horizontal resin table to irradiate the target area with X rays. Irradiation conditions: the source target distance is 1m, the energy is 6MeV, and the dosage rate is 400 cGy/min. The abdominal cavity of the mouse is irradiated locally by adopting different irradiation doses, and each group of mice respectively receives irradiation of 2.0, 4.0, 8.0, 12.0 and 16.0 Gy. Local irradiation of the abdominal cavity of a mouse with different irradiation doses can cause the aggravation of the intestinal injury along with the increase of the irradiation dose. According to the research, an eyeball of a Balb/c mouse is picked and blood is collected on the 5 th day after irradiation, the whole blood of the mouse is obtained and then is placed for 4 hours at the temperature of 4 ℃, after blood coagulation, the upper layer serum is separated into a new centrifugal tube with the volume of 1.5ml after centrifugation at 3000rpm and 4 ℃ for 10 minutes, and the upper layer serum is stored at the temperature of-20 ℃ to be detected. After blood collection, the mice were sacrificed by cervical dislocation, tissues of a jejunal segment of 10cm were cut, the small intestine was washed with 1ml of PBS, stored on ice, centrifuged at 3000rpm for 5min, and the supernatant was taken to obtain an intestinal fluid diluent. Stored at 4 ℃ for detection on the same day.
Observing the change of cell nucleus and cytoplasm of villus in small intestine of Balb/c mice and the expression level of HMGB1 protein in intestinal fluid and serum 5 days after 2, 4, 8, 12 and 16Gy X-ray irradiation, analyzing the relation between HMGB1 and irradiation dose, and analyzing the effect of HMGB1 in radioactive small intestine injury; detecting the secretion amount of inflammatory factors such as IL-6 in serum, and analyzing the correlation between HMGB1 secretion and radiation-induced small intestine injury.
Example 2 Change in the content of HMGB1 in the intestinal juice of mice after X-ray intraperitoneal irradiation
As shown in figure 1, on the 5 th day after the abdominal cavity and the pelvic cavity of Balb/c mice are irradiated by X rays, the content of HMGB1 in intestinal fluid is detected by an ELISA method, and the content of HMGB1 in the intestinal fluid can be detected to be improved along with the increase of irradiation dose and the aggravation of small intestine injury. 2Gy irradiation can increase the HMGB1 content in the mouse small intestine diluent by about 28.4pg/ml and improve the HMGB1 content by 1.5 times; compared with the unirradiated mice, the content of HMGB1 in mouse intestinal diluent is increased by 93.5, 137.6, 166.7 and 177.0pg/ml respectively and is increased by about 2.6 times, 3.3 times, 3.8 times and 4.0 times respectively under the irradiation of 4, 8, 12 and 16 Gy. This is probably because the X-ray ionizing radiation can cause the HMGB1 in the epithelial nucleus of the small intestine to be transferred to the extracellular direction, wherein a part of HMGB1 is transferred through the capillary vessel of the central axis of the villus and the lymphatic capillary to cause the inflammatory reaction of the surrounding tissues or the whole body, and another part of HMGB1 is directly secreted into the intestinal fluid, and HMGB1 in the intestinal fluid is used as an inflammatory promoter to induce the inflammatory reaction of the section of small intestine, so that the small intestine releases more HMGB1, thereby aggravating the radiation injury. After the injury reaches a certain degree, the original HMGB1 in the small intestine mucosal epithelial cell nucleus is completely transferred, and the small intestine mucosal epithelial cell is apoptotic or necrotic and loses the regeneration capability, so that the new HMGB1 can not be regenerated, and the content of the HMGB1 in the intestinal fluid of the mouse is not increased after the injury of high-dose radiation. Pathological results show that after 16Gy irradiation, the villus sense of small intestine villi disappears, the villus structure is incomplete, and only a few residual glandular and mucosal epithelial cells proliferate; this is in contrast to the altered content of HMGB1 in the intestinal fluid of the irradiated mice in this experiment.
Example 3 Change in relative expression of HMGB1 in mouse intestinal villus cells following X-ray Abdominal radiation
As shown in fig. 2, the expression level of HMGB1 in the nucleus of the intestinal villus cells decreased with the increase of the irradiation dose after irradiation, and when the irradiation dose reached 12Gy, only a very small amount of HMGB1 was present in the nucleus. In cytoplasm, the expression level of HMGB1 is increased after 2Gy irradiation, and it is presumed that the increased HMGB1 may be derived from the outward transfer of HMGB1 in the nucleus, and at the moment, the HMGB1 in cytoplasm is not completely secreted extracellularly; however, when the irradiation dose was increased to 4Gy, HMGB1 in the cytoplasm began to decrease at a level substantially identical to that of HMGB1 in the cytoplasm of a normal mouse subjected to false irradiation. As can be seen from the above results, the ionizing radiation can induce the transition of HMGB1 in the mucosa of the small intestine from the inside of the nucleus to the cytoplasm and gradually secrete it into the extracellular fluid, and the transition amount and the secretion amount thereof increase with the increase of the irradiation dose; when the irradiation dose reached 8Gy, only a small amount of HMGB1 was present in the nucleus and cytoplasm; only a very small amount of HMGB1 remained in the cells when the irradiation dose reached 12-16 Gy. The result can be mutually verified with HMGB1 in serum and intestinal fluid, and proves that HMGB1 in small intestine cell nucleus is transferred and secreted into extracellular fluid in a large amount along with the increase of irradiation dose to play an extracellular inflammatory role, and when the dose reaches 12Gy, the HMGB1 in small intestine cell nucleus and cytoplasm almost completely disappears, and more HMGB1 cannot be secreted into the extracellular fluid.
Example 4 changes in HMGB1 in mouse serum following X-ray intraperitoneal irradiation
As shown in FIG. 3, when Balb/c mice were irradiated by X-ray abdominal cavity on day 5, the HMGB1 content in the serum increased with the increase of the irradiation dose and the aggravation of the small intestine injury; when the mouse is irradiated in 2Gy, although the content of HMGB1 in the serum of the mouse is increased, the difference has no statistical significance compared with a 0Gy group; when the X-ray irradiation dose is 4, 8, 12 and 16Gy, the content of HMGB1 in the serum of the mouse is rapidly increased, the content is respectively increased by about 1010.4, 1185.0, 1584.8 and 1625.7pg/ml, the content is increased by about 2.5, 2.7, 3.3 and 3.4 times, and the rising trend of the content of HMGB1 in the serum of the mouse in the 16Gy group is slowed down.
Example 5 IL-6 changes in mouse serum following X-ray intraperitoneal irradiation
IL-6 can be elevated under the induction of HMGB1 in the extracellular fluid, exacerbating the inflammatory response. As shown in FIG. 4, after 2-16Gy X-ray intraperitoneal irradiation, as the content of HMGB1 in mouse serum is gradually increased, the secretion amount of inflammatory factor IL-6 in the mouse serum is also increased along with the increase of irradiation dose and HMGB1, and is consistent with the rising trend of HMGB1 in the serum. As shown in FIG. 4, the level of IL-6 detectable in the serum of normal mice was about 0.6 pg/ml; on the 5 th day after 2, 4, 8, 12 and 16Gy X-ray irradiation, the content of HMGB1 in the serum of the mice rapidly increases, increases by about 1.1, 2.0, 4.8, 5.7 and 5.9pg/ml respectively, increases by about 2.7, 4.1, 8.3, 9.8 and 10.1 times, and the content of HMGB1 in the serum of the mice in the 16Gy group is reduced. Therefore, 2-16Gy X-ray abdominal cavity single irradiation can cause a large amount of inflammatory factor IL-6 to be secreted, so that the in-vivo inflammatory reaction is aggravated; the increase of IL-6 is induced by the extracellular release of HMGB1 induced by ionizing radiation, which acts as an inflammatory factor.
Example 6 changes in HMGB1 in mouse feces after X-ray intraperitoneal irradiation
5 Balb/c mice are used in each group, after anesthesia, the abdominal cavity of the mice is irradiated locally by adopting 4, 8, 12 and 16Gy X-rays with the energy of 160KeV and the dose rate of 100 cGy/min. On day 5 post-irradiation, both 4G y and 8Gy mice excreted feces, only 3 mice in 12Gy had feces, and 5 mice in 16Gy (1 death; 4 extreme wilts, arch back) had no feces. 0.1g of fresh feces from each mouse was removed, diluted with 1ml of PBS buffer, vortexed for 30 seconds, centrifuged at 3000rpm for 15min, and 50. mu.l of supernatant was collected and assayed for HMGB1 content in the feces of the mice after irradiation by ELISA.
After being irradiated by X-rays, HMGB1 in damaged intestinal cells is translocated and secreted from cell nuclei outwards, and intestinal fluid and feces which most directly reflect secretion of HMGB1 in the intestinal tract are obtained. Stool sampling is relatively convenient and non-invasive, so that the stool is taken as a sample for detecting the content change of HMGB 1. As shown in fig. 5, after 4-12 Gy of X-ray irradiation, the content of HMGB1 in feces increases with the increase of irradiation dose, about 5.7 μ g of HMGB1 can be detected in normal mice per gram of feces, and average detectable HMGB1 in 4, 8, 12Gy irradiated mice per gram of feces increases with the increase of irradiation dose, about 12.6, 21.7, 25.3 μ g; mice with extremely high HMGB1 appeared in both 8Gy and 12Gy irradiation groups, and the median of the HMGB1 content in feces of each group also showed an increasing trend, namely 5.6. mu.g (0Gy group), 10.7(4Gy group), 12.1(8Gy group), and 17.2(12Gy group), respectively. The results are combined with the pathological detection results, so that after 4, 8 and 12Gy of X-rays are irradiated, the damage of the mouse small intestinal mucosa is aggravated, and HMGB1 in intestinal cells subjected to radiation damage is secreted into an intestinal cavity and is discharged along with excrement. About 80% of mice which are irradiated by X-ray over 4Gy in the abdominal cavity have the content of HMGB1 more than 10 mu g in per gram of excrement. Therefore, whether the mice are subjected to radioactive small intestine injury can be marked by detecting the HMGB1 content in the feces of the irradiated mice.
Claims (9)
1. A method for marking radioactive damage of small intestine by using HMGB1 is characterized in that the method is used for marking the radioactive damage of small intestine by using HMGB1 to translocate in nucleus and cytoplasm of small intestine mucosa or HMGB1 to release in small intestine fluid and peripheral blood.
2. The method according to claim 1, characterized in that it consists in detecting the content of HMGB1 in the serum.
3. The method according to claim 2, wherein the serum HMGB1 content is increased by 501.7-2315.3pg/ml by 1.7-3.4 fold.
4. The method according to claim 1, characterized in that the method is used for detecting the content of HMGB1 in intestinal fluid.
5. The method according to claim 4, wherein the amount of intestinal juice HMGB1 is increased by 28.4-177.0pg/ml by a factor of 1.4-4.0.
6. A labeling method for the radioactive damage of the small intestine is characterized in that the method is used for detecting the content of an IL-6 inflammatory factor in serum.
7. The method according to claim 6, wherein the serum IL-6 content is increased by 1.1-5.9pg/ml by a factor of 2.7-10.1.
8. A method according to claim 1, characterized in that it is a method for determining the content of HMGB1 in faeces.
9. A method according to claim 8, wherein the stool contains HMGB1 in an amount greater than 2-fold and greater than 10 μ g/g.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102170898A (en) * | 2008-09-30 | 2011-08-31 | 伊纳特治疗有限公司 | Compositions and methods for treatment of radiation exposure |
| CN104487066A (en) * | 2012-07-23 | 2015-04-01 | 国立大学法人东京大学 | Prophylactic and/or therapeutic agent for radiation damage |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102170898A (en) * | 2008-09-30 | 2011-08-31 | 伊纳特治疗有限公司 | Compositions and methods for treatment of radiation exposure |
| CN104487066A (en) * | 2012-07-23 | 2015-04-01 | 国立大学法人东京大学 | Prophylactic and/or therapeutic agent for radiation damage |
Non-Patent Citations (4)
| Title |
|---|
| JING SHI等: "Protective effects of seabuckthorn pulp and seed oils against radiation-induced acute intestinal injury" * |
| KEON-IL IM等: "Regulation of HMGB1 release protects chemoradiotherapy-associated mucositis" * |
| 王利利: "HMGB1在电离辐射损伤中的作用与相关机制研究" * |
| 魏雨露 等: "血根碱对小鼠放射肠损伤防护作用及其机制研究" * |
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