CN107831315A - Transferrins mark and its application - Google Patents
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- CN107831315A CN107831315A CN201711044659.7A CN201711044659A CN107831315A CN 107831315 A CN107831315 A CN 107831315A CN 201711044659 A CN201711044659 A CN 201711044659A CN 107831315 A CN107831315 A CN 107831315A
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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
- G01N33/6893—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
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- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/28—Neurological disorders
- G01N2800/2871—Cerebrovascular disorders, e.g. stroke, cerebral infarct, cerebral haemorrhage, transient ischemic event
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/32—Cardiovascular disorders
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
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- G01N2800/323—Arteriosclerosis, Stenosis
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Abstract
The invention belongs to Medical Molecular Biology technical field, and in particular to a kind of transferrins (transferrin) mark related to the morbidity of hypoferric anemia, apoplexy and atherosclerosis disease and its application.Application of the transferrins mark of the present invention in hypoferric anemia, apoplexy and atherosclerosis early diagnosis kit is prepared.Application of the transferrins mark of the present invention as drug targets and/or therapeutic targets in treatment apoplexy, atherosclerosis or other cardiovascular and cerebrovascular diseases associated medicines are prepared.The present invention is using transferrins as hypoferric anemia, apoplexy and atherosclerosis disease mark specificity and sensitiveness height, and detection method is simple.There is good effect to apoplexy and atherosclerosis or other cardiovascular and cerebrovascular diseases associated treatments using transferrins as drug targets and/or therapeutic targets simultaneously, the apoplexy and atherosclerosis of anti-human or animal can be used for, imply that fabulous prospect in medicine.
Description
Technical field：
The invention belongs to Medical Molecular Biology technical field, and in particular to a kind of transferrins mark and its application.
Background technology：
Iron deficiency (iron deficiency, ID) is to refer mainly to hemoglobin content, red blood cell number and the red blood cell pressure in blood
Product is less than the pathological state of normal value, and wherein hypoferric anemia (iron-deficiency anemia, IDA) is most common poor
Blood (anemia), have impact on the whole world about 2,000,000,000 population (N.J.Kassebaum, R.Jasrasaria, M.Naghavi,
S.K.Wulf,N.Johns,R.Lozano,M.Regan,D.Weatherall,D.P.Chou,T.P.Eisele,
S.R.Flaxman,R.L.Pullan,S.J.Brooker,C.J.Murray,A systematic analysis of global
The to 2010.Blood123,615-624 (2014) of anemia burden from 1990 and E.McLean, M.Cogswell,
I.Egli,D.Wojdyla,B.de Benoist,Worldwide prevalence of anaemia,WHO Vitamin and
Mineral Nutrition Information System,1993-2005.Public health nutrition 12,
444-454(2009)).In recent years, the research based on crowd showed the patient's cardio-cerebralvascular diseases easily occurred frequently for suffering from IDA, such as
Phlebothrombosis (venous thrombus), apoplexy (stroke) and atherosclerosis (atherosclerosis) etc.
(P.T.Akins,S.Glenn,P.M.Nemeth,C.P.Derdeyn,Carotid artery thrombus associated
with severe iron-deficiency anemia and thrombocytosis.Stroke 27,1002-1005
(1996), D.S.Har transferrins ield, N.J.Lowry, D.L.Keene, J.Y.Yager, Iron deficiency:a
cause of stroke in infants and children.Pediatric neurology 16,50-53(1997)、
J.M.Coutinho,S.M.Zuurbier,A.E.Gaartman,A.A.Dikstaal,J.Stam,S.Middeldorp,
S.C.Cannegieter,Association Between Anemia and CerebralVenous Thrombosis:
Case-Control Study.Stroke 46,2735-2740(2015)、T.Nagai,N.Komatsu,Y.Sakata,
Y.Miura,K.Ozawa,Iron deficiency anemia with marked thrombocytosis complicated
by central retinal vein occlusion.Internal medicine 44,1090-1092(2005)、
M.Aslan,M.Kosecik,M.Horoz,S.Selek,H.Celik,O.Erel,Assessment of paraoxonase
and arylesterase activities in patients with iron deficiency
Anemia.Atherosclerosis 191,397-402 (2007) and M.A.Bari, M.A.Rahman, Effect of iron
deficiency anemia on the development of atherosclerosis in
chicks.Atherosclerosis 21,401-408(1975)).Up to the present, patient's IDA cardio-cerebralvascular diseases occurred frequently
The reason for be still unclear.
Cardiovascular and cerebrovascular disease is the general designation of cardiovascular and cranial vascular disease, is referred to because hyperlipidemia, blood are sticky, dynamic
The ischemic or hemorrhagic disease that heart, brain and body tissue caused by pulse atherosclerosis, hypertension etc. occur.Wherein,
The formation of high thrombophilia or thrombus plays important role in the pathogenic process of cardiovascular and cerebrovascular disease.Cardiovascular and cerebrovascular
Disease seriously endangers human health and the phenomenon increased year by year is presented in such disease incidence.《Chinese cardiovascular disease report 2016》It is aobvious
It has been the dead the first reason of Chinese residents to show cardiovascular and cerebrovascular disease.Recent studies indicate that some and cardiovascular and cerebrovascular disease mark
The generation of will thing and such disease is substantially related.The research for cardiovascular and cerebrovascular disease occurring Research of predicting markers can be cardiovascular and cerebrovascular disease
The early diagnosis of disease provides important clue and foundation, while cardiovascular and cerebrovascular disease label is as the potential of such disease treatment
Target provides new thinking for the treatment of such disease.Conventional tag thing such as T-CHOL, low-density lipoprotein (LDL) are high
Density lipoprotein (HDL) is the cardio-cerebralvascular diseases mark of most study in recent years.
Transferrins (transferrin) is iron protein main in blood plasma, the molecular weight about 7.7 of transferrins
Ten thousand, it is responsible for iron and the iron discharged of being degraded by red blood cell that delivery is absorbed by digest tube for single chain glycoprotein.Transferrins in blood plasma
Concentration adjusted by iron supply, in iron deficiency state, plasma transferrins concentration rise, returned to just after iron is effectively treated
Ordinary water is put down.The physiological function of transferrins, except the function with transhipment iron ion, also has anti-in research display at this stage
Bacterium, participate in the critical function such as Growth and Differentiation of cell (P.T.Gomme, K.B.McCann, J.Bertolini, Transferrin:
structure,function and potential therapeutic actions.Drug Discovery Today 10,
267-273(2005)).But the other application report on transferrins is few.
The content of the invention：
Present invention discover that turn in hypoferric anemia, ishemic stroke and Atheromatosis human plasma containing substantial amounts of
Ferritin, find that low iron feed can be with the expression of transferrins in inducing mouse body by zoopery.By building mouse blood
Such disease and expression of transferrin height correlation are found in bolt model, headstroke model and Atherosclerosis Model.Turn iron
The rise of protein concentration is related to the morbidity of cardiovascular and cerebrovascular disease, the concentration of the invention by detecting transferrins in patient's blood plasma
It is used as diagnosis and the monitoring mark of the early stage of the cardio-cerebralvascular diseases such as hypoferric anemia, apoplexy and atherosclerosis.Together
When, using transferrins as drug targets and/or therapeutic targets, preparing transferrin antibodies using by way of Antybody therapy
Or other modes for reducing expression of transferrin eliminate the elevated transferrins energy of content in cardio-cerebralvascular diseases pathogenic process
Enough morbidities for significantly mitigating such disease further deteriorate, prompt transferrins can be used as apoplexy, atherosclerosis or
The key target of other cardio-cerebralvascular diseases treatment.
An object of the present invention is to provide a kind of related to the morbidity of hypoferric anemia, apoplexy and atherosclerosis disease
Transferrins mark.
It is athero- in preparation hypoferric anemia, apoplexy and artery that second object of the present invention is to provide transferrins mark
Application in hardened early diagnostic kit.
Described diagnostic kit includes the special rabbit polyclonal antibody of the anti-rotation ferritin that we prepare.The kit is also
Including 96 orifice plates, coating buffer, confining liquid, cleaning solution, horseradish peroxidase-labeled anti-rabbit IgG antibody secondary antibody, colour developing bottom
The conventional Enzyme-linked Immunosorbent Assay reagent such as thing, terminate liquid.
The use process of mentioned reagent box is as follows：It is coated with after the plasma sample for collecting obtained patient is diluted with coating buffer
In 96 orifice plates, by using the specific antibody absorption transferrins in the sample of anti-rotation ferritin after sample well Seal treatment
On, establish chromogenic reaction eventually through the secondary antibody of horseradish peroxidase-labeled.By extrapolating institute with standard curve contrast
The concentration of transferrins in test sample sheet.Lacked according to the height of transferrin concentrations come the order of severity for the morbidity that diagnoses the illness, realization
Iron anaemia, apoplexy, atherosclerosis or the purpose of other cardio-cerebralvascular diseases early diagnosis.
Third object of the present invention is that transferrins mark is preparing treatment as drug targets and/or therapeutic targets
Application in apoplexy, atherosclerosis or other cardiovascular and cerebrovascular diseases associated medicines.
The beneficial effects of the present invention are：Using transferrins as hypoferric anemia, apoplexy and atherosclerosis mark
Thing specificity and sensitiveness are high, and detection method is simple.Drug targets and/or therapeutic targets centering are used as using transferrins simultaneously
The treatment of wind, atherosclerosis or other cardio-cerebralvascular diseases has good effect, imply that fabulous prospect in medicine.
Brief description of the drawings：
Fig. 1 is the enzyme-linked immunosorbent assay knot of transferrin concentrations in ischemic stroke patients blood plasma provided by the invention
Fruit is schemed；Wherein, ischemic stroke patients and the investigation quantity of normal person are respectively 453 and 341 samples in Fig. 1-A；Fig. 1-B show
Show the western blot experimental results of transferrin concentrations in ischemic stroke patients blood plasma；Fig. 1-C represent the system to Fig. 1-B
Result is counted, the statistical result is from 5 experimental results independently repeated.**p<0.01；
Fig. 2 is the enzyme-linked immunosorbent assay of transferrin concentrations in Atheromatosis human plasma provided by the invention
Result figure；Wherein, the investigation quantity of Fig. 2-A atherosclerosis patient and normal person are all 42 samples；Fig. 2-B are artery
The western blot experimental results of transferrin concentrations in atheromatosis human plasma；Fig. 2-C represent the statistics knot to Fig. 2-B
Fruit, the statistical result is from 5 experimental results independently repeated.*p<0.05.
Fig. 3 is the enzyme of transferrins in low iron feed inducing mouse provided by the invention and high ferro feed inducing mouse blood plasma
Join immunoadsorption assay result figure.**p<0.01.
Fig. 4 is FeCl provided by the invention3The mouse carotid thrombosis illustraton of model of induction；Wherein, Fig. 4-A displays turn iron egg
White overexpression and its tail vein injection (30mg/kg) are to FeCl3The blood flow monitoring experiment of the mouse carotid thrombosis model of induction；
Fig. 4-B show that transferrins is overexpressed and its tail vein injection (30mg/kg) is to FeCl3The mouse carotid thrombosis model of induction
Form the HE dyeing of the Vascular Slice of thrombi；Fig. 4-C displays are counted (n with the perfusion unit benchmark of blood flow to Fig. 4-A
=6)；(n=is counted to Fig. 4-B on the basis of the percentage that Fig. 4-D displays account for intravascular space cross section by thrombosis area
6)。**p<0.01。
Fig. 5 is cerebral ischemic model result figure provided by the invention；Wherein, Fig. 5-A are that transferrins is overexpressed and its tail is quiet
Arteries and veins injects the influence result figure of (30mg/kg) to focal cerebral ischemia model；Fig. 5-B are using the percentage that brain infarction area accounts for as base
It is accurate that statistical results chart (n=6) is carried out to Fig. 5-A；Fig. 5-C are to carry out Bederson appraisal result figures to each group mouse.**p<
0.01。
Fig. 6 is mouse thoracic aortic atherosclerosis result figure provided by the invention；Wherein, Fig. 6-A mouse aorta pectoralis is cut
Piece carries out the result figure of oil red-O dyeing；Fig. 6-B are to account for whole arterial root to Fig. 6-A result figures progress oil red-O stained areas to cut
The statistical results chart (n=6) of piece area percentage.**p<0.01.
Fig. 7 is atherosclerosis Antybody therapy result figure provided by the invention；Wherein, Fig. 7-A represent Apoe-/-Mouse
Only feed high lipid food and Apoe-/-Mouse gives Antitransferrin antibody (high lipid food+turn while high lipid food is fed
Ferritin antibody), while give after IgG Isotype controls (high lipid food+antibody morphism control) are treated and aorta pectoralis is cut
Piece carries out the result figure of oil red-O dyeing；Fig. 7-B represent that carrying out oil red-O stained areas to Fig. 7-A accounts for whole arterial root sliced surfaces
The statistical chart (n=6) of product percentage.**p<0.01.
Embodiment：
The present invention is elaborated below in conjunction with the accompanying drawings, the effect of embodiment only illustrates rather than the restriction present invention.
Embodiment 1：
Transferrins detection kit.
The assay method is conventional enzyme-linked immunosorbent assay for measuring (ELISA), and brief step is as follows：1 μ l are taken respectively
Ischemic stroke patients after 1000 times of dilutions, hypoferric anemia patient, Atheromatosis people and human normal plasma and 99 μ
Added after l fixers (50mM carbonate buffer solutions, pH 9.6) mixing in 96 hole microwell plates (Nunc, Denmark) plate hole, 4 DEG C of coatings
Overnight.Next day, solution in hole is discarded, Seal treatment is carried out after washing 3 times with 0.1M phosphate buffers, added afterwards homemade anti-
Transferrins rabbit polyclonal antibody (10 μ g/ml) is incubated 60 minutes under the conditions of 37 DEG C.Washing adds after removing uncombined antibody
Enter the anti-rabbit IgG secondary antibodies (KPL, the U.S.) of horseradish peroxidase-labeled, finally with tetramethyl benzidine (TMB) develop the color instead
Should.Done standard curve with a series of by the standard transferrins of gradient dilution and tried to achieve the dense of transferrins in determined plasma sample
Degree.
Embodiment 2：
Transferrins in hypoferric anemia patient, ischemic stroke patients, Atheromatosis people and human normal plasma
The measure of content.
3.8% sodium citrate 1 is collected from hospital：Above-mentioned patient's blood plasma (ischemic stroke patients, the n=453 of 9 anti-freezings；Lack
Iron anaemia patient, n=452；Atheromatosis people, n=42；Normal person, n=341) examined according to the method for embodiment 1
Survey transferrin contents.As a result it is respectively shown in such as Fig. 1-A, Fig. 2-A, ischemic stroke patients, hypoferric anemia patient and dynamic
Obvious rise phenomenon (p is presented in the concentration level of transferrins in pulse atherosclerosis patient's blood plasma<0.01).
Embodiment 3：
Transferrins in hypoferric anemia patient, ischemic stroke patients, Atheromatosis people and human normal plasma
The western blot detections of content.
General proteins electrophoresis (SDS-PAGE) is carried out after above-mentioned 10 times of dilutions of patient's blood plasma, it is rear to carry out western blot inspections
Survey.Experiment carries out western blot detections using homemade transferrin antibodies.Gained after Western blot results are taken pictures
Image is analyzed with Image J softwares.As a result such as Fig. 1-B, C, Fig. 2-B, C are respectively shown in, ischemic stroke patients, iron-deficient
Obvious rise phenomenon (p is presented in the concentration level of transferrins in anaemia patient and Atheromatosis human plasma<0.01).
Embodiment 4：
Transferrin content detects in low iron inducing mouse blood plasma.
C57BL/6J mouse are respectively through too low iron feed (Fe<10mg/kg) and high ferro feed (Fe>90mg/kg) lure respectively
With the transferrin content in the ELISA method detection mice plasma of embodiment 1 after leading 30 days.As a result it is low as Fig. 3 is respectively shown in
Obvious rise phenomenon (p is presented in the concentration level of transferrins in the mice plasma of iron feed induction<0.01).
Embodiment 5：
In order to further verify transferrins and thrombotic correlation, we pass through the transferrins slow virus of structure
Over-express vector (pLVX-Puro vector, Clontech, USA) makes in mouse (C57BL/6J mice, 28-30g) blood plasma
Transferrin raises the transferrins made with the mode of Tail Vein injection Mouse transferrins (30mg/kg) in mice plasma
Content raises.Experiment is by detecting FeCl3The influence that the thrombus model detection transferrins of induction is inclined to mouse thrombus.Its
In, FeCl3The thrombus model of induction be respectively with 10% FeCl3(w/v) lead to after inducing neck arteries difference 5min, 10min
Laser-Doppler is crossed to detect the blood flow at the position and take the position blood vessel to carry out frozen section and carry out HE dyeing.As a result it is：Phase
For control group, (M turns iron egg for transferrins overexpression group (PLP- transferrins) and mouse Transferrin tail vein injection group
- 30mg/kg in vain) neck arteries thrombus showed increased, blood flow slow down (shown in Fig. 4-A-D, p<0.01).
Embodiment 6：
Influence of the transferrins to focal cerebral ischemia model.
According to embodiment 5 method we pass through the transferrins slow virus over-express vector (pLVX-Puro of structure
Vector, Clontech, USA) make that Transferrin in mouse (C57BL/6Jmice, 28-30g) blood plasma raises and tail is quiet
The mode of arteries and veins injection mouse Transferrin (30mg/kg) raises the transferrin content in mice plasma.After anesthesia, neck center
Otch successively cuts mouse skin and hypodermis, separates nutator, cuts off anterior belly of digastric, exposure right carotid
(CCA), internal carotid (ICA) and external carotid artery (ECA), condense arteria thyreoidea and arteria pharyngea on ECA using electric coagulating apparatus and cut
It is disconnected.ECA distal end is ligatured, and in its proximal part hanging wire, temporarily folder closes CCA and ICA, cuts ECA, by line bolt from ECA stumps
ICA is inserted, ligatures ECA stumps, removes ICA artery clamp, inwardly top is slowly advanced by ICA.Appropriate adjustment direction, is inserted into
Line bolt mark (calculates 10mm) from CCA crotches, removes line bolt after 30min, is sewed up the incision after observing no active bleeding.It is whole
Individual process is incubated with electric blanket, and temperature is 36~37 DEG C.Wherein, administration time is 20min tail vein injection phases after insertion line bolt
Close medicine.Brain is taken to carry out 2%TTC dyeing after 12 hours：Deep anaesthesia mouse, broken end is injected intraperitoneally using 3% yellow Jackets
Brain is peeled off, removes olfactory bulb and brain stem, -20 DEG C of freezing 10-30min are immediately placed in after normal saline flushing, takes out, is placed in brain mould
In tool, 4-5 pieces are laterally cut, lucifuge dyeing 10-30min, 4% paraformaldehyde in 37 DEG C of 2%TTC is immersed and fixes, take pictures, calculate brain
Infarction volume.As a result it is：Relative to control group, transferrins overexpression group and transferrins tail vein injection group mouse cerebral infarction
Area it is bigger (shown in Fig. 5-A-C, p<0.01).
Embodiment 7：
In order to further verify the correlation of transferrins and incidence of atherosclerosis, we are to Apoe-/-Mouse enters
Row high lipid food feed while by inject be overexpressed or strike low phase close virus intervened, the specific packet of sample and
Administering mode is as follows：Control group (NC, physiological saline group), transferrins overexpression group (PLP- transferrins), transferrins strike
Low group (RNR- transferrins) viral administering mode tail vein injection virus quantity is 107TU (transducing units), high fat
Induction time is 6 weeks.Experiment mice takes arterial root to carry out oil red-O dyeing after cutting into slices to mark mouse aorta root tissue to cut
Fat in piece.Oil red-O painted areas sizes represent the size of athero- spot and the order of severity of incidence of atherosclerosis.
Determine athero- spot area and the aortic root vessel cross-sections gross area with image analysis software Image J, and calculate atheromatous plaque/
Aortic root vessel cross-sections gross area ratio.As a result it is：Relative to control group (physiological saline group), transferrins overexpression group
(PLP- transferrins) can be obviously promoted atheromatous plaque increase, and transferrins strikes low group (RNR- transferrins) and can substantially pressed down
Atheromatous plaque processed increases (Fig. 6-A, B, p<0.01).
Embodiment 8：
In order to verify whether transferrins mark can be used as drug targets and/or therapeutic targets preparing treatment artery
Application in terms of anti-atherosclerotic agent, we are on the one hand by Apoe-/-Mouse carry out high lipid food feed respectively 2,4,6 weeks (2WK,
4WK, 6WK) to promote the incidence of atherosclerosis of this group of mouse, on the other hand pass through while high lipid food is continuously fed
The mode of tail vein injection using transferrins as therapeutic targets give Antitransferrin antibody treatment (HFD+ transferrins AB,
Only, weekly administration is twice by 50 μ g/), while give the IgG Isotype controls (HFD+IgG) of equivalent.Antybody therapy will be above-mentioned after terminating
Two groups of experiment mices take arterial root to carry out oil red-O dyeing after cutting into slices according to the methods described of embodiment 7, small to compare this two groups
The order of severity of mouse AS disease incidences.As a result it is：Relative to the AS morbidity mouse (NC) for only feeding high lipid food, pass through anti-rotation iron
Phenomenon (Fig. 7-A, B, p significantly reduced is presented in the athero- spot area of mouse aorta root position after protein antibodies treatment<
0.01).The above results, which are clearly demonstrated using transferrin antibodies as drug targets and/or therapeutic targets, passes through Antybody therapy
Mode atherosclerosis disease is treated after can significantly suppress the morbidity of atherosclerosis disease.
Described above is only the preferred embodiment of the present invention, it is noted that for the ordinary skill people of the art
For member, under the premise without departing from the principles of the invention, some improvements and modifications can also be made, these improvements and modifications also should
It is considered as protection scope of the present invention.
Claims (3)
- A kind of 1. transferrins mark related to the morbidity of hypoferric anemia, apoplexy and atherosclerosis disease.
- 2. transferrins mark described in claim 1 is preparing hypoferric anemia, apoplexy and atherosclerosis early diagnosis Application in kit.
- 3. transferrins mark described in claim 1 is preparing treatment apoplexy, artery as drug targets and/or therapeutic targets Application in atherosis or other cardiovascular and cerebrovascular diseases associated medicines.
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Cited By (2)
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| CN111257568A (en) * | 2020-02-24 | 2020-06-09 | 中国科学院昆明动物研究所 | Application of reagent for detecting transferrin expression quantity in preparation of intestinal immune tolerance imbalance disease diagnosis reagent or kit |
| CN111879949A (en) * | 2020-08-05 | 2020-11-03 | 中国科学院昆明动物研究所 | Application of substance for detecting or regulating lactoferrin expression quantity in preparation of medicine or kit for preventing and/or treating cardiovascular and cerebrovascular diseases |
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| 杨威: "尿转铁蛋白与冠状动脉粥样硬化性心脏病及冠状动脉狭窄程度关系的研究", 《检验医学与临床》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111257568A (en) * | 2020-02-24 | 2020-06-09 | 中国科学院昆明动物研究所 | Application of reagent for detecting transferrin expression quantity in preparation of intestinal immune tolerance imbalance disease diagnosis reagent or kit |
| WO2021169035A1 (en) * | 2020-02-24 | 2021-09-02 | 中国科学院昆明动物研究所 | Applications of transferrin expression-detecting reagent in preparing diagnostic reagent or reagent kit for intestinal immune tolerance disorders |
| CN111879949A (en) * | 2020-08-05 | 2020-11-03 | 中国科学院昆明动物研究所 | Application of substance for detecting or regulating lactoferrin expression quantity in preparation of medicine or kit for preventing and/or treating cardiovascular and cerebrovascular diseases |
| CN111879949B (en) * | 2020-08-05 | 2021-11-09 | 中国科学院昆明动物研究所 | Application of substance for detecting or regulating lactoferrin expression quantity in preparation of medicine or kit for preventing and/or treating cardiovascular and cerebrovascular diseases |
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