Applications of interferon regulatory factor 1 gene in treatment of atherosclerosis

An atherosclerosis and gene technology, applied in gene therapy, pharmaceutical formulations, antibodies, etc., can solve the problems of biological functions and possible mechanisms of action that have not yet been elucidated, and achieve the effect of promoting atherosclerosis

Inactive Publication Date: 2015-01-07
WUHAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Based on the above research basis, we believe that IRF1 may play an important role in the early characteristic pathophysiological process of atherosclerosis, but it

Method used

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  • Applications of interferon regulatory factor 1 gene in treatment of atherosclerosis
  • Applications of interferon regulatory factor 1 gene in treatment of atherosclerosis
  • Applications of interferon regulatory factor 1 gene in treatment of atherosclerosis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0044] Example 1 Mouse Atherosclerosis Model (AS) Obtained

[0045] 1. Grouping of experimental animals: ApoE- / - mice and IRF1- / -ApoE- / - mice aged 8 weeks, weighing 19-25g, male, were given high-fat diets (Western Diets, HFD) and low-fat diets, respectively. Feed (Normal chow, NC) feeding, ApoE- / - HFD group, ApoE- / - NC group, IRF1- / -ApoE- / - HFD group, IRF1- / -ApoE- / - NC group, a total of 4 groups, 20 in each group.

[0046] 2. Atherosclerosis model induced by high-fat diet:

[0047] ApoE- / - mice and IRF1- / -ApoE- / - mice were used to establish AS models, and phenotype correlation analysis was performed to clarify the role of IRF1 gene in atherosclerotic diseases. From the age of 8 weeks, the mice in the HFD group were sacrificed after 28 weeks of high-fat diet, and the samples were collected in the NC group after 28 weeks of low-fat diet.

Embodiment 2

[0048] Example 2 Determination of plaque area in AS model mice

[0049] 1. Final mouse tissue harvesting

[0050] Mice were fed with high-fat or low-fat diet until 28 weeks, weighed, anesthetized with 3% pentobarbital sodium, 90 mg / kg, fixed on the sampling board with a needle, moistened the skin of the chest and abdomen of the mouse with gauze, and used Ophthalmic scissors cut open the chest cavity, expose the heart, cut open the right atrial appendage, insert the needle of the infusion set into the left ventricle, inject 10-15mL PBS buffer slowly with a 50mL syringe, wait until the right atrial appendage effluent is clear, replace it with 4% Polymer Formaldehyde continued to inject 10-15mL. After the perfusion, the thoracoabdominal viscera were removed and only the heart was kept. Put the mouse under a microscope, separate the fascia and adipose tissue around the aortic arch, cut off the brachiocephalic trunk, put it into a 5mL EP tube filled with 4% paraformaldehyde, cut ...

Embodiment 3

[0065] Example 3 Determination of Plaque Stability in AS Model Mice

[0066] 1. Area Size Determination of the Center of Aortic Sinus Necrosis

[0067] For hematoxylin and eosin staining (HE staining), the method is the same as in Example 2.4, and a tissue containing cholesterol crystals and no nucleus fiber structure is selected to take pictures under a microscope.

[0068] Determination of the area of ​​the necrosis center: use Image-Pro Plus 6.0 image analysis software to circle the area of ​​the necrosis center.

[0069] 2. Determination of collagen content in aortic sinus:

[0070] Sirius Red (PSR) staining, the main steps are: bake at 55°C for 30 minutes → xylene for 2 minutes, 3 times → 100% alcohol for 1 minute → 95% alcohol for 1 minute → 70% alcohol for 1 minute → rinse with running water for 10 minutes → double distilled water for 1 minute → mass fraction 0.2% phosphomolybdic acid for 2 minutes → 0.1% Sirius scarlet picric acid solution was dropped on the tissue, ...

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Abstract

The invention discloses applications of an interferon regulatory factor 1 gene in treatment of atherosclerosis, belonging to the field of the functions and applications of a gene. An atherosclerosis model is obtained by taking ApoE-/-mice and IRF1-/-ApoE-/-mice as experimental objects through induction of high-fat diet, results show that the IRF1 gene defects markedly reduce the plaque area of the aorta, enhance the stability of aortic sinus plaque, and markedly lighten the inflammatory response compared with the ApoE-/-mice. The function of the IRF1 in the atherosclerosis is mainly reflected by the fact that the IRF1 achieves the effect of promoting the formation of the aortic plaque, especially the effect of promoting the atherosclerosis. Aiming to the functions of the IRF1, the IRF1 can be used as a drug target for screening drugs preventing, alleviating and/or treating atherosclerosis, and an inhibitor of the IRF1 can be used for preparing a drug for preventing, alleviating and/or treating atherosclerosis.

Description

technical field [0001] The invention belongs to the field of gene function and application, and specifically relates to the function and application of an interferon regulatory factor 1 (IRF1) gene in the treatment of atherosclerosis, specifically, the IRF1 gene is used in the preparation of prevention, alleviation and / or treatment of atherosclerosis Drug application in sclerosis. Background technique [0002] Cardiovascular and cerebrovascular diseases are the main cause of death in many developed countries, and the morbidity and mortality in my country are also increasing year by year. The basis of cardiovascular and cerebrovascular diseases is atherosclerosis (Atheosclersis, AS). Atherosclerosis can thicken and harden the arterial wall and narrow the lumen, leading to many cardiovascular and cerebrovascular events. Acute stenosis and occlusion of coronary arteries caused by rupture of atherosclerotic unstable plaques, platelet aggregation, and thrombus formation are impo...

Claims

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Application Information

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IPC IPC(8): A61K48/00A61K39/395A61P9/10
Inventor 李红良蒋丁胜黄玲张晓晶
Owner WUHAN UNIV
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