CN103784975A - Function of IRF (Interferon Regulatory Factor) 7 in atherosclerosis and application of inhibitor of IRF7 - Google Patents

Function of IRF (Interferon Regulatory Factor) 7 in atherosclerosis and application of inhibitor of IRF7 Download PDF

Info

Publication number
CN103784975A
CN103784975A CN201410031612.7A CN201410031612A CN103784975A CN 103784975 A CN103784975 A CN 103784975A CN 201410031612 A CN201410031612 A CN 201410031612A CN 103784975 A CN103784975 A CN 103784975A
Authority
CN
China
Prior art keywords
irf7
apoe
mice
atherosclerosis
gene
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CN201410031612.7A
Other languages
Chinese (zh)
Other versions
CN103784975B (en
Inventor
李红良
王丕晓
向梅
邓克穷
胡俊飞
黄玲
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Wuhan Huikang Gene Technology Co.,Ltd.
Original Assignee
Wuhan University WHU
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Wuhan University WHU filed Critical Wuhan University WHU
Priority to CN201410031612.7A priority Critical patent/CN103784975B/en
Publication of CN103784975A publication Critical patent/CN103784975A/en
Application granted granted Critical
Publication of CN103784975B publication Critical patent/CN103784975B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Landscapes

  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Plant Substances (AREA)

Abstract

The invention discloses the function of an IRF7 gene in atherosclerosis and an application of an inhibitor of the IRF7 gene, belonging to the field of the function and the application of a gene. According to the invention, ApoE-/-mice and IRF7-/-ApoE-/-mice are taken as experimental subjects, AS model mouse plaque area measurement and inclusion analysis are performed through a high fat induced atherosclerosis model, and the results show that the aorta plaque area of the IRF7-/-ApoE-/-mice is remarkably reduced in comparison with that of the ApoE-/-mice. The invention discloses the function of the IRF7 gene in an atherosclerosis disease, which is mainly means that the IRF7 gene has an effect of promoting formation of the aorta plaques, especially that the IRF7 gene can worsen the atherosclerosis. According to the abovementioned function, the IRF7 can be used as a drug target for screening drugs for treating the atherosclerosis disease. The inhibitor of the IRF7 can be used for preparing the drug for treating the atherosclerosis disease.

Description

The function of IRF7 gene in atherosclerosis and the application of inhibitor thereof
?
Technical field
The invention belongs to function and the application of gene, particularly a kind of IRF7(interferon regulatory factor 7) function of gene in atherosclerosis and the application of inhibitor thereof.
Background technology
Cardiovascular and cerebrovascular disease is the main lethal cause of disease in many developed countries, also raises year by year in sickness rate and the fatality rate of China.The basis of cardiovascular and cerebrovascular disease is atherosclerosis (Atheosclersisis, AS), and atherosclerosis can make that ductus arteriosus wall thickens, hardening, luminal stenosis, causes a lot of cardiocerebrovasculaevents events to occur.And the acute Stricture and occlusion of coronary artery that the breaking of atherosclerosis unstable spot, hematoblastic gathering and thrombosis cause is the major reason that causes acute coronary syndrome (acute coronary syndrome, ACS).
Atherosclerosis is multiple gene, the common a kind of chronic inflammation disease participating in of risk factor and immunologic mechanism, inflammatory and immune response local and whole body plays an important role in atherosclerosis generation evolution, inherent immunity and adaptive immunity participate in regulating atherosclerotic lesion jointly, on pathology, show as large, medium-sized artery many places Mottling formation, be apt to occur in blood shunt, the regions such as tremulous pulse bending and arterial branch, its characteristics of lesion is that in blood, lipid deposits at endarterium, cause inner membrance kitchen range fibrous thickening, focus deep is the medicated porridge sample material being formed by slough and extracellular lipid pond.In atheromatous plaque, exist panimmunity cell, wherein common with macrophage and T cell, in addition also has a small amount of dendritic cell (Dentritic cell, DC), natural killer cell (natural killer cell, NK cell) and mastocyte (mast cell) etc., bone-marrow-derived lymphocyte occasionally had.
The macroscopic damage of atherosclerosis earliest period is lipid striped, is mainly made up of the Macrophage derived foamy cell that has absorbed a large amount of cholesterol.Mononuclear cell in blood circulation is attached to active endotheliocyte at tremulous pulse damageable zone, has started the formation of lipid striped, and the attraction that the mononuclear cell sticking is subject to the local chemistry producing to ingratiate with molecule subsequently moves under inner membrance, and is further divided into macrophage.A large amount of cholesterol esters, in macrophage inner accumulated, form foam cell, and this is the early stage characteristic pathophysiological process of atherogenesis.Atherosclerotic is multifactor coefficient result.The dangerous factor of atherosclerosis of having found is at present a lot, but related pins is all undesirable to treatment and control effect, and blood fat reducing and anti-inflammatory treatment are current topmost treatment measures.Increasing evidence shows that immunoreation participates in the links of progression of atherosclerosis, and the gene pairs control atherosclerosis of therefore exploring regulation and control immune cell function is significant.
Interferon (interferon, IFN) is the cytokine that a class has several functions, has broad-spectrum disease resistance cytotoxic activity, is the first line of defence of body opposing viral infection; Also there is important effect the aspects such as immunity monitoring, inhibition cell proliferation and the immunoregulation to cancerous cell.The most important function of interferon regulatory factor is generation, the induction body antiviral effect of induction IFN, with and effect in IFN signal pathway.IRF7 is a member in interferon regulatory factor (interferon regulatory factor, IRF) family, there are some researches show that IRF7 and tumor, hepatitis, autoimmune disease etc. have close relationship.
Summary of the invention
For addressing the deficiencies of the prior art and deficiency, the object of the present invention is to provide the application in the medicine of preparation treatment atheromatosis of a kind of IRF7 and inhibitor thereof.
Object of the present invention is achieved through the following technical solutions:
The present invention is with ApoE gene knockout (ApoE -/-) mice and the dual-gene (IRF7 that knocks out of IRF7/ApoE -/-apoE -/-) mice is experimental subject, induced and obtained atherosclerosis mouse model (AS) model by high fat diet, carried out AS model mice plaque area and measured and inclusions analysis, result shows and ApoE -/-mice contrast, IRF7 -/-apoE -/-mice atherosclerosis Aortic Plaque area is starkly lower than the ApoE that feedstuff of the same race is raised -/-mice.This prompting IRF7 gene knockout can suppress atherosclerotic generation, illustrates that IRF7 gene can worsen atherosclerotic generation, provides theoretical foundation and Clinical Basis for studying the atherosclerotic novel targets of control and New Policy.
The function of IRF7 gene in atherosclerosis, be mainly reflected in IRF7 gene have worsen Aortic Plaque form effect, particularly IRF7 have worsen atherosclerotic effect.
For the above-mentioned functions of IRF7, provide IRF7 application in the medicine of screening inhibition Aortic Plaque formation as drug targets.
For the above-mentioned functions of IRF7, provide IRF7 application in the medicine of screening treatment atheromatosis as drug targets.
For the above-mentioned functions of IRF7, provide the inhibitor of IRF7 in the application of preparing in the medicine that suppresses Aortic Plaque formation.
Suppress the medicine that Aortic Plaque forms, the inhibitor that comprises IRF7.
For the above-mentioned functions of IRF7, provide the inhibitor of IRF7 in the application of preparing in the medicine for the treatment of atheromatosis.
Treat a medicine for atheromatosis, the inhibitor that comprises IRF7.
The inhibitor of described IRF7 is preferably the siRNA of IRF7 gene, the rna interference vector of IRF7 gene, and the antibody of IRF7 and other can suppress the one in inhibitor that IRF7 expresses.
Result of study of the present invention shows, IRF7 -/-apoE -/-mice is in the atherosclerosis of high fat diet induction, with ApoE -/-mice is compared, and Aortic Plaque area obviously reduces and collagen content increases, and illustrates that IRF7 gene has important deterioration effect in atheromatosis model.
The present invention has following advantage and effect with respect to prior art:
(1) the present invention finds the new function of IRF7 gene, and IRF7 gene has the effect that worsens atheromatosis.
(2) effect in deterioration atheromatosis based on IRF7, it can be the drug provision target of development atheromatosis, and the inhibitor of IRF7 can be used for the atherosclerotic medicine of preparation treatment.
Accompanying drawing explanation
Fig. 1 is ApoE -/-and IRF7 -/-apoE -/-mouse Weight result of variations figure (zero difference between NS representative group).
Fig. 2 is ApoE -/-and IRF7 -/-apoE -/-the speckle coloration result figure of mice; A is mouse aorta tree oil red O stain figure and plaque area statistics block diagram; B is ApoE -/-and IRF7 -/-apoE -/-mouse aorta hole HE colored graph and plaque area statistics block diagram.
Fig. 3 is ApoE -/-and IRF7 -/-apoE -/-the analysis result figure of the speckle inclusions of mice; A is ApoE -/-and IRF7 -/-apoE -/-the macrophage mark (CD68) of mice and smooth muscle cell mark (SMA) immunofluorescence dyeing and result statistics block diagram (in figure, m represents aortic tunica media, and L represents aorta tube chamber); B is ApoE -/-and IRF7 -/-apoE -/-the Picro-Sirius red dyeing of mice and result statistics block diagram.
The specific embodiment
Below in conjunction with embodiment and accompanying drawing, the present invention is described in further detail, but embodiments of the present invention are not limited to this.
Animal for research and raising:
Laboratory animal kind, sex, age in week and source: ApoE gene knockout (ApoE -/-) mice and the dual-gene (IRF7 that knocks out of IRF7/ApoE -/-apoE -/-) mice, male, 8 week age, body weight 19-25g.ApoE knock out mice (ApoE -/-mice, C57BL/6J background, purchased from Jackson Laboratory, article No. 002052).IRF7 -/-apoE -/-mice by IRF7 knock out mice (IRF7 knock out mice, C57BL/6J background, purchased from RIKEN BRC company, BRC numbering: RBRC01420) and ApoE knock out mice hybridize and obtain.
Laboratory animal feed formula: high lipid food (HFD, purchased from Fukang bio tech ltd of China, Beijing, by AIN-76 A Western Diets formula, percent of calories: protein 15.8%, fat 40%, carbohydrate 44.2%); Low fat feedstuff (NC, purchased from Fukang bio tech ltd of China, Beijing, article No. D12450B): percent of calories: protein 20%, carbohydrate 70%, fat 10%.
Animal feeding and environmental condition: all experiment mices are all raised at the SPF of angiocardiopathy institute of Wuhan University level Animal House (credit number: SYXK(Hubei Province): 2009-0053).Alternately illumination in every 12 hours, 24 ± 2 ℃ of temperature, humidity 40%-70%, the mice feed of freely drinking water.
Embodiment 1 mice Atherosclerosis Model (AS) obtains
1. laboratory animal grouping: select 8 week age, body weight 19-25g, male, ApoE -/-mice and IRF7 -/-apoE -/-mice, gives respectively high lipid food (Western Diets, HFD) and low fat feedstuff (Normal chow, NC) and raises, ApoE -/-hFD group, ApoE -/-nC group, IRF7 -/-apoE -/-hFD group, IRF7 -/-apoE -/-nC group totally 4 groups.
2. Atherosclerosis Model is induced operating process by high lipid food:
Adopt ApoE -/-mice and IRF7 -/-apoE -/-mice, sets up AS model, carries out phenotype correlation analysis, specifies IRF7 gene pairs incidence of atherosclerosis and plays a significant role.Mice since 8 week age feed for nursing until within 28 weeks, put to death and collect sample.
Embodiment 2 AS model mice plaque area are measured
1. mice last tissue sampling eventually
Mice is fed high lipid food until 28 weeks time, weigh, and uses 3% pentobarbital sodium, 90mg/kg anesthetized mice, be fixed on material drawing board with syringe needle, with the moistening mice skin of chest abdomen of gauze, cut off thoracic cavity with eye scissors, expose heart, cut off right auricle, the syringe needle of transfusion device is lunged to left ventricle, slowly inject 10-15mL PBS buffer with 50mL syringe, treat that right auricle effluent is limpid, change 4% paraformaldehyde and continue to inject 10-15mL.After perfusion finishes, remove splanchnocoel internal organs, only retain heart.Mice is placed under microscope, separate aortic arch fascia, fatty tissue around, cut brachiocephalic trunk, put into the 5mlEP pipe that 4% paraformaldehyde is housed, cut heart in ascending aorta initial part, cut off at thoracic aorta middle part, and under neck summation clavicle, cut off at about 3mm place, and aortic arch is put into above-mentioned EP pipe.
2. aorta tree plaque area is measured
Aorta tree be placed in 4% paraformaldehyde overnight fixing → pure water rinsing 30min → 60% isopropyl alcohol processes 10 min → oil red O dye liquor and dyes 60 min → 60% isopropyl alcohol 1min × 3 time to removing remaining outer wall fat → tremulous pulse dye is laid on black dissection stencil plate under clean background → anatomical lens, after dyeing, take pictures with digital camera, and use IPP image analysis software to carry out plaque area quantitative assay.(oil red O stock solution=0.5 gram oil red O+100 milliliter 100% isopropyl alcohol, oil red O dye liquor (working solution): V(oil red O stock solution)/V(H 2o)=3/2)
Aorta tree plaque area (%)=speckle gross area/aorta tree gross area * 100%.
3. pathological tissue processing
3.1 paraffin specimen
Heart preparation is taken out after overnight fixing in 4% paraformaldehyde, brachiocephalic trunk, aortic arch is carefully wrapped with filter paper, in case spill from embedding frame gap.Flowing water is put into dewaterer, 30% ethanol 15min → 50% ethanol 15min → 75% ethanol 15min → 85% ethanol 15min → 95% ethanol 15min → 100% ethanol 15min → 100% ethanol 15min → dimethylbenzene 15min → dimethylbenzene 15min → paraffin 30min → paraffin 30min after rinsing 30min.After brachiocephalic trunk and aortic arch have dewatered, take out from dewaterer.Brachiocephalic trunk is Y and stands in paraffin, and aortic arch lies low in paraffin.
3.2 aortic tissue sections
Wax stone is fixed in the holder of section on head, adjusts to and slightly leaves on the position that section can switch to, and wax stone organizes tangent plane and the section edge of a knife to want vertical parallel, adjusts slice thickness (5 microns).The slice, thin piece cutting, the right hand clamps firm paraffin section gently with curved tweezers, left hand takes off section with dry brush pen from section, put into the glass dish of containing warm water (approximately 30 ℃), and section is spread out on warm water face, the tangent plane of light is downward, slice in thermostatted water, fully spread out and flatten after (being approximately no more than for 10 seconds), microscope slide is vertically inserted in water light by section, and will cut into slices one side group on slide with tweezers, and the position of adjusting section, with uprightly mentioning by slide.On the ground glass of slide one end, write specimen numbering with pencil.Section is dried and spent the night.
4. aortic sinus plaque area is measured
Haematoxylin Yihong dyeing (HE dyeing): 65 ℃ of white sheets of paraffin toast 30 minutes → dimethylbenzene, 5 minutes × 3 times → 100% ethanol 1 minute → 95% ethanol 1 minute → 70% ethanol 1 minute → pure water rinsing (not hang with the globule on slide as standard) → the get rid of moisture on most microscope slide, haematoxylin solution (Zhuhai shellfish rope, BA-4021) contaminate 5 minutes → tap water rinsing (removing haematoxylin loose colour on slide) → 1% acidic alcohol 1-3 second → tap water rinsing (removing acidic alcohol on slide) → Scott liquid (sodium bicarbonate 0.35g, magnesium sulfate 2g, distilled water 100ml) 1 minute → tap water embathes (removing the Scott liquid on slide) → get rid of moisture being all on slide, Yihong solution (Zhuhai shellfish rope, BA-4024) dyeing 10 seconds → pure water rinsing (removing the loose colour in Yihong on slide) → 70% ethanol once → 95% ethanol once → 100% ethanol 30 seconds, 3 times → dimethylbenzene 2 minutes, 3 times → take advantage of dimethylbenzene when not dry mounting (often taking out a front cover opens, take section without bubble as principle) → microscope takes pictures.Directly with IPP image analysis software circle aortic sinus plaque area (mm 2).
In order whether to observe IRF7 to ApoE -/-the basic body weight of mice exerts an influence, and we have surveyed the body weight of each group of mice.The demonstration of Fig. 1 result, HFD organizes ApoE -/-the body weight of mice will be apparently higher than its NC group, and no matter NC group or HFD group, the ApoE in group -/-mice and IRF7 -/-apoE -/-mice Body weight average no significant difference, shows that IRF7 gene does not affect ApoE -/-the body weight change of mice.
Set by aorta that oil red O stain can assess that atheromatous plaque forms substantially number, distribution situation and plaque area size.Fig. 2 A is oil red O stain result figure after mice AS model, and scalp is done and aortic root is the most obvious position of atheromatous plaque.Fig. 2 B is HE coloration result figure after mice AS model, and result shows, with ApoE -/-mice is compared, IRF7 -/-apoE -/-in mouse aorta tree, plaque area obviously reduces, IRF7 -/-apoE -/-mouse aorta hole plaque area obviously reduces, and shows that the disappearance of IRF7 gene can significantly reduce the size of atheromatous plaque.
The analysis of embodiment 3 AS model mice speckle inclusions
1. macrophage and smooth muscle cell are expressed and are measured
Immunofluorescence dyeing detects the expression of macrophage (CD68), smooth muscle actin (Smooth Muscle Actin, SMA).Required primary antibodie information: CD68 (MCA1957; 1:100; Rat; AbD Serotec), SMA (ab5694; 1:100; Rabbit; Abcam); Required two anti-information: Alexa Flour 568 goat anti-rat IgG (A11077; Invitrogen, Carlsbad, CA), Alexa Fluor 488-conjugated goat anti-rabbit IgG (A11008; Invitrogen, Carlsbad, CA).
Key step is:
1) roasting sheet: more than paraffin section is placed in to baking box 30min.
2) dewaxing: dimethylbenzene 5min × 3 time.
3) hydration: 100% ethanol 5min × 2 time; 95% ethanol 5min; 70% ethanol 5min; ddH 2o embathes 5min × 2 time.
4) citrate tissue antigen recovery (Pressure method): get a certain amount of pH6.0 citrate antigen retrieval working solution in repairing box, necessary enough whole sections of submergence of amount of repair liquid, put into by repairing box the pressure cooker that adds appropriate tap water, big fire is heated to boiling, tissue slice after dewaxing hydration is placed on high temperature resistant staining rack, again staining rack is slowly put into and repaired box, cover pot cover, buckle pressure valve, continue to be heated to jet, start after timing 5min pressure cooker deenergization, go valve to uncap, take out and repair box; Room temperature is taken out section after placing 20min natural cooling.
5) ddH 2o rinsing 5min × 2 time, PBS rinsing 5min × 2 time.
6) groupization stroke circle, drips 10% sheep blood serum (GTX27481, GeneTex) sealing, 37 ℃ of sealing 60min in wet box.
7) abandon confining liquid, drip the primary antibodie of proper proportion dilution, 4 ℃ of overnight incubation, 37 ℃ of rewarming 30min, discard primary antibodie, and PBS washes 10min × 3 time.
8) drip two and resist, in wet box, hatch 60min for 37 ℃, discard two and resist, PBS embathes 5min × 3 time.
9) SlowFade Gold antifade reagent with DAPI(S36939, Invitrogen) mounting.
10) fluorescence Microscopic observation, takes pictures.Preserve 4 ℃ of preservations in dark wet box if need.
Fluorescence statistical method: SMA(%) the positive absorbance/speckle gross area of the interior SMA of=speckle * 100%; CD68(%) the positive absorbance/speckle gross area of CD68 * 100% in=speckle.
2. Picro-Sirius red (PSR) dyeing
Key step is: 55 ℃ of baking 30min → dimethylbenzene 2min, 3 times → 100% ethanol 1min → 95% ethanol 1min → 70% ethanol 1min → flowing water rinses 10min → distilled water 1min → mass fraction 0.2% phosphomolybdic acid 2min → 0.1% sirius red picric acid solution and drips in tissue, 90min → removal residual liquid → 0.01N hydrochloric acid 4s → 70% ethanol 1 time → 90% ethanol 1 time → 100% ethanol 30s dyes in wet box, 3 times → dimethylbenzene 2min, 3 times → take advantage of the not dry coverslip immediately of dimethylbenzene mounting, microscope is taken pictures.
Statistical method: the former positive gross area/speckle gross area * 100% of collagen (%)=speckle hose lining.
Smooth muscle cell can be secreted various kinds of cell substrate, is the cell source of atheromatous plaque endocrine collagen, thereby Main Function is to repair destroyed cellular matrix composition to play a protective role; Macrophage is most important cell component in speckle, it mainly contains blood circulation mononuclear cell and enters and interiorly differentiate after subcutaneous, Monocytes/Macrophages can be secreted multiple adhesion, chemotactic factor as cell adhesion molecule (ICAM-1), MCAF (MCP-1) etc., promote entering of speckle inner cell, in addition macrophage also can be secreted multiple matrix metalloproteinase (MMPs), reduce area of collagen in speckle, thereby destroy the stability of speckle; Collagen composition is most important extracellular matrix in speckle, is also the main component of fibrous cap, there is anti-blood flow and impact the effect that prevents plaque rupture, and be also the important evaluation index of safeguarding plaque stability.
Fig. 3 is ApoE -/-and IRF7 -/-apoE -/-the analysis result figure of the speckle inclusions of mice.For the expression of macrophage in detection of plaque and smooth muscle cell, CD68(macrophage mark is carried out respectively in aortic sinus section by we) and SMA(smooth muscle cell mark) etc. immuning fluorescent dyeing analysis macrophage and smooth muscle cell composition.Immunofluorescence is sent out and is observed SMA, CD68 at ApoE -/-mice and IRF7 -/-apoE -/-in mice speckle, all have expression, SMA is at IRF7 -/-apoE -/-in mice speckle, expression is apparently higher than ApoE -/-mice; CD68 is at IRF7 -/-apoE -/-in mice speckle, expression is significantly lower than ApoE -/-mice (A); PSR coloration result shows the model after high fat diet, IRF7 -/-apoE -/-the collagen ratio of group mice is apparently higher than ApoE -/-mice, illustrates IRF7 -/-apoE -/-the speckle more stable (B) of group mice.Result shows that IRF7 gene knockout can reduce speckle inner area in AS model, the stability of protection speckle.
Above-described embodiment result shows, ApoE -/-mice and IRF7 -/-apoE -/-mice issues lively pulse atherosclerosis in the induction of high fat diet.IRF7/ApoE is dual-gene knock out after, mouse aorta plaque area is compared with ApoE -/-little remarkable minimizing.These results suggest, IRF7 gene can promote formation and atherosclerotic development of Aortic Plaque.The present invention has proved that IRF7 gene has important deterioration effect in Atherosclerosis Model, and it can be used as the medicine of drug targets screening treatment atheromatosis.
Above-described embodiment is preferably embodiment of the present invention; but embodiments of the present invention are not restricted to the described embodiments; other any do not deviate from change, the modification done under spirit of the present invention and principle, substitutes, combination, simplify; all should be equivalent substitute mode, within being included in protection scope of the present invention.

Claims (7)

  1. Application in the medicine that 1.IRF7 forms at screening inhibition Aortic Plaque as drug targets.
  2. 2.IRF7 is the application in the medicine of screening treatment atheromatosis as drug targets.
  3. Application in the medicine that the inhibitor of 3.IRF7 forms at preparation inhibition Aortic Plaque.
  4. 4. suppress the medicine that Aortic Plaque forms, it is characterized in that: the inhibitor that comprises IRF7.
  5. The application of the inhibitor of 5.IRF7 in the medicine of preparation treatment atheromatosis.
  6. 6. a medicine for the treatment of atheromatosis, is characterized in that: the inhibitor that comprises IRF7.
  7. 7. according to the medicine described in the application described in claim 3 or 5 or claim 4 and 6, the inhibitor that it is characterized in that described IRF7 is the one in siRNA, the rna interference vector of IRF7 gene or the antibody of IRF7 of IRF7 gene.
CN201410031612.7A 2014-01-23 2014-01-23 Function of IRF (Interferon Regulatory Factor) 7 in atherosclerosis and application of inhibitor of IRF7 Active CN103784975B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201410031612.7A CN103784975B (en) 2014-01-23 2014-01-23 Function of IRF (Interferon Regulatory Factor) 7 in atherosclerosis and application of inhibitor of IRF7

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201410031612.7A CN103784975B (en) 2014-01-23 2014-01-23 Function of IRF (Interferon Regulatory Factor) 7 in atherosclerosis and application of inhibitor of IRF7

Publications (2)

Publication Number Publication Date
CN103784975A true CN103784975A (en) 2014-05-14
CN103784975B CN103784975B (en) 2015-07-15

Family

ID=50661307

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201410031612.7A Active CN103784975B (en) 2014-01-23 2014-01-23 Function of IRF (Interferon Regulatory Factor) 7 in atherosclerosis and application of inhibitor of IRF7

Country Status (1)

Country Link
CN (1) CN103784975B (en)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104258419A (en) * 2014-09-29 2015-01-07 武汉大学 Applications of interferon regulatory factor 1 gene in treatment of atherosclerosis
CN114557318A (en) * 2022-03-28 2022-05-31 中山大学 Non-alcoholic steatohepatitis mouse model construction method based on PEDF/LDLR double gene knockout and application

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
QIMINGLIANG ET AL.: "negative regulation of irf7 activation by activating transcription factor 4 suggests a cross-regulation between the ifn responses and the cellular integrated stress responses", 《THE JOURNAL OF IMMUNOLOGY》, 8 December 2010 (2010-12-08) *
吴丹等: "炎症体研究进展", 《中国细胞生物学学报》, vol. 35, no. 10, 31 December 2013 (2013-12-31) *
陈煌峰等: "toll样受体4与冠状动脉粥样硬化关系的研究进展", 《J CLIN CARDIOL》, vol. 24, no. 5, 31 May 2008 (2008-05-31) *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104258419A (en) * 2014-09-29 2015-01-07 武汉大学 Applications of interferon regulatory factor 1 gene in treatment of atherosclerosis
CN114557318A (en) * 2022-03-28 2022-05-31 中山大学 Non-alcoholic steatohepatitis mouse model construction method based on PEDF/LDLR double gene knockout and application

Also Published As

Publication number Publication date
CN103784975B (en) 2015-07-15

Similar Documents

Publication Publication Date Title
JP5749651B2 (en) Compounds and methods for reducing mobilization and / or migration of polymorphonuclear cells
Puzzolo et al. Structural, ultrastructural, and morphometric study of the zebrafish ocular surface: a model for human corneal diseases?
CN103784975B (en) Function of IRF (Interferon Regulatory Factor) 7 in atherosclerosis and application of inhibitor of IRF7
CN103784971B (en) Function of IRF (Interferon Regulatory Factor) 3 gene in atherosclerosis and application of inhibitor of IRF3 gene
CN103784973B (en) The function and application of IRF9 gene in atherosclerosis
Dobutr et al. The effects of edible bird’s nest on T-lymphocyte proliferation, secondary lymphoid organs, and interleukin-2 production
CN104225627B (en) The leukocytic immunity globulin sample receptor subfamily B member 4 function and application in treatment atherosclerosis
Lahnsteiner Differences in immune components of blood, spleen and head kidney between diploid and auto-and allotriploid Salmonidae
CN116898970A (en) Application of ATP5D activator and B lymphocyte in preparation of medicines
CN103784943B (en) Function and application of interferon regulatory factor 4 (IRF4) in scaffold and endarterectomy restenosis
Takiyama et al. Visual capability of the weakly electric fish Apteronotus albifrons as revealed by a modified retinal flat-mount method
CN103784945B (en) Function and application of IRF3 (Interferon Regulatory Factor 3) to restenosis after stenting and carotid endarterectomy
CN104258419A (en) Applications of interferon regulatory factor 1 gene in treatment of atherosclerosis
CN104198697B (en) Centrifugal force and shear stress response gene 1(RECS1) treating the function and application in angiostenosis after damage
CN104258395B (en) Functions and applications of nucleotide synthetase CAD in treatment of atherosclerosis
CN104232732B (en) The function and application of MAPK signal integrating kinase 2 in treatment atherosclerosis
Mallory Scarlet fever. Protozoon-like bodies found in four cases
CN111194724B (en) Function and application of Sh3rf2 in preparation of medicine for treating non-alcoholic fatty liver disease and/or type II diabetes
CN104324390B (en) The application in treatment atherosclerosis of the Mindin gene
CN104225597A (en) Function and application of MAPK (mitogen-activated protein kinase) signal-integrating kinase 1 in treatment of atherosclerosis
CN104324389B (en) The blood shearing force response protein 1 function and application in treatment atherosclerosis
CN107157980A (en) Purposes of the Oridonin in anti-myocardial remodelling medicament is prepared
CN104383561A (en) Function and application of signal regulatory protein 1 treating atherosclerosis
CN104324388A (en) Application of interferon regulatory factor 4 gene in treatment of atherosclerosis
CN104096219A (en) Function and application of II type oncostatin M acceptor (OSMR) in treatment of fatty liver and II type diabetes

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C14 Grant of patent or utility model
GR01 Patent grant
TR01 Transfer of patent right

Effective date of registration: 20191122

Address after: 430040 No.1, floor 1, No.17, eleven village, Changqing Garden, Dongxihu District, Wuhan City, Hubei Province (18)

Patentee after: Wuhan Dafeng Biotechnology Co., Ltd

Address before: 430072 Hubei Province, Wuhan city Wuchang District of Wuhan University Luojiashan

Patentee before: WuHan University

TR01 Transfer of patent right
TR01 Transfer of patent right

Effective date of registration: 20191218

Address after: 430014 3119, floor 3, building 9, Guanggu science and technology port, 18 huashiyuan North Road, Donghu New Technology Development Zone, Wuhan City, Hubei Province

Patentee after: Wuhan linyijia Gene Technology Co., Ltd

Address before: 430040 No.1, floor 1, No.17, eleven village, Changqing Garden, Dongxihu District, Wuhan City, Hubei Province (18)

Patentee before: Wuhan Dafeng Biotechnology Co., Ltd

TR01 Transfer of patent right
CP03 Change of name, title or address

Address after: 430076 room 002, 16 / F, building D2, phase III, software new town, No. 8, Huacheng Avenue, Wuhan East Lake New Technology Development Zone, Wuhan, Hubei Province

Patentee after: Wuhan Huikang Gene Technology Co.,Ltd.

Address before: Room 3119, 3 / F, building 9, Guanggu science and technology harbor, 18 huashiyuan North Road, Donghu New Technology Development Zone, Wuhan City, Hubei Province, 430014

Patentee before: Wuhan linyijia Gene Technology Co.,Ltd.

CP03 Change of name, title or address