Application of interferon regulatory factor 4 gene in treatment of atherosclerosis

A technology of atherosclerosis and regulatory factors, applied in gene therapy, pharmaceutical formulations, drug combinations, etc., can solve the problems of biological functions and possible mechanisms of action that have not yet been elucidated

Inactive Publication Date: 2015-02-04
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 IRF4 may play an important role in the early characteristic pathophysiological process of atherosclerosis, but it

Method used

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  • Application of interferon regulatory factor 4 gene in treatment of atherosclerosis
  • Application of interferon regulatory factor 4 gene in treatment of atherosclerosis
  • Application of interferon regulatory factor 4 gene in treatment of atherosclerosis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0042] Example 1 Mouse Atherosclerosis Model (AS) Obtained

[0043] 1. Grouping of experimental animals: ApoE- / - mice and IRF4- / -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, IRF4- / -ApoE- / - HFD group, IRF4- / -ApoE- / - NC group, a total of 4 groups, 20 in each group.

[0044] 2. Atherosclerosis model induced by high-fat diet:

[0045] ApoE- / - mice and IRF4- / -ApoE- / - mice were used to establish AS models, and phenotype correlation analysis was performed to clarify the role of IRF4 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

[0046] Example 2 Determination of plaque area in AS model mice

[0047] 1. Final mouse tissue harvesting

[0048] 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

[0063] Example 3 Determination of Plaque Stability in AS Model Mice

[0064] 1. Area Size Determination of the Center of Aortic Sinus Necrosis

[0065] 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.

[0066] 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.

[0067] 2. Determination of collagen content in aortic sinus:

[0068] 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 a function and an application of an interferon regulatory factor 4 (IRF4) gene in treatment of atherosclerosis and belongs to the field of functions and applications of genes. In the invention, an ApoE -/- mouse and an IRF4 -/- ApoE -/- mouse are employed as experimental subjects and an atherosclerosis model is obtained through high-fat diet induction. A result proves that compared with the ApoE -/- mouse, an IRF4 gene defect can significantly increase a plague area in aorta, reduce stability of aortic sinus plagues and significantly deteriorate an inflammatory response, which indicate that the IRF4, in the atherosclerosis, mainly has effects of inhibiting formation of a plague in the aorta and especially inhibiting the atherosclerosis. On the basis of the functions hereinabove of the IRF4, the IRF4 can be used for preparing a drug for preventing, alleviating and/or treating the 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 interferon regulatory factor 4 (IRF4) in the treatment of atherosclerosis. application in medicines. 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 important causes of acute coronary syndrome (ACS). [0003] Atherosclerosis is a chronic inflammatory disease involving multiple genet...

Claims

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Application Information

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IPC IPC(8): A61K48/00A61P9/10
Inventor 李红良蒋丁胜邓克穷张晓晶
Owner WUHAN UNIV
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