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Application of interferon regulatory factor 9 (IRF9) and inhibitor thereof in coronary arteriosclerotic heart disease

A technology of inhibitors and RNA interference, applied in the field of gene function and application, can solve problems such as not being able to meet needs

Active Publication Date: 2014-05-14
WUHAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the various drugs currently used clinically have certain limitations and cannot meet the needs.

Method used

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  • Application of interferon regulatory factor 9 (IRF9) and inhibitor thereof in coronary arteriosclerotic heart disease
  • Application of interferon regulatory factor 9 (IRF9) and inhibitor thereof in coronary arteriosclerotic heart disease
  • Application of interferon regulatory factor 9 (IRF9) and inhibitor thereof in coronary arteriosclerotic heart disease

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] [Example 1] Myocardial ischemia / reperfusion injury (MIRI) model was obtained

[0039] 1. Grouping of experimental animals: male C57BL / 6 strain mice (WT) and IRF9 gene knockout mice (KO) were used to create a model of myocardial ischemia / reperfusion injury by ligation of the left anterior descending coronary artery (LAD) of the mouse heart. Randomly divided into 4 groups, each group: C57BL / 6 strain mouse sham operation group (WT SHAM) and I / R operation group (WT MI), IRF9 gene knockout mouse sham operation group (KO SHAM) and I / R group surgery group (KO MI).

[0040] 2. The I / R model uses ligation of the left anterior descending coronary artery (LAD) of the mouse heart to cause myocardial ischemia / reperfusion injury. The model operation process:

[0041] 2.1 Weighing and skin preparation for anesthesia: Accurately weigh the body weight (g) of the mouse in dynamic mode with an electronic balance, accurately prepare 3% pentobarbital sodium solution with double distilled w...

Embodiment 2

[0049] [Example 2] 2,3,5-Triphenyltetrazolium chloride (2,3,5-Triphenyltetrazolium chloride, TTC)-Evans blue (Evans blue) double staining to measure myocardial infarct size

[0050] After 24 hours of ischemia-reperfusion, mice were anesthetized by intraperitoneal injection of 80 mg / kg pentobarbital sodium solution, the chest cavity was cut open, the aorta was separated, and the heart was cut together with the aorta. The needle was inserted into the root of the ascending aorta, not passing through the aortic valve, and ligated and fixed. Prepare 3-4 mL of TTC phosphate buffer (PH=7.4) at 37°C and slowly perfuse the heart from the aorta, and stop the injection when the myocardium turns brick red. Ligate the LAD again, and then perfuse about 2mL of 2.5% Evans blue evenly and slowly through the aorta, and make the myocardial ischemic area face up to prevent the outflowing Evans blue from contaminating the heart surface. After the heart turns blue, the perfusion is stopped and ful...

Embodiment 3

[0055] [Example 3] Detection of cardiac function in myocardial ischemia-reperfusion model mice

[0056] 1 PV detection of hemodynamics

[0057] 1.1 Preliminary preparation

[0058] (1) Anesthesia machine preparation: first connect the oxygen cylinder and the air inlet port on the anesthesia machine, then unscrew the sealing cap of the dosing port on the anesthesia machine, quickly add isoflurane to the safety scale, and then tighten the sealing cap. Unscrew the main valve on the oxygen cylinder, adjust the knob of the flow control valve, and maintain the outlet pressure at 0.2-0.3mPa.

[0059] (2) Preparation of the mice to be tested: After the mice to be tested were quickly anesthetized with isoflurane, the hair on the left chest area was shaved, and the head of the treated mice was inserted into the anesthetic catheter sleeve, and treated with 1.5-2.0% isoflurane Alkane maintains a stable anesthesia in mice.

[0060] 1.2 PV detection

[0061] After disinfection with iodi...

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Abstract

The invention discloses an application of interferon regulatory factor 9 (IRF9) and an inhibitor thereof in coronary arteriosclerotic heart disease, belonging to the field of gene functions and applications. According to the application disclosed by the invention, IRF9 gene knockout mice are taken as experimental subjects, and a myocardial ischemia-reperfusion injury model is constructed by ligating mouse heart left anterior descending (LAD) artery; results show that compared with a wild type (WT) mouse, the IRF9 gene knockout mouse has the characteristics that the myocardial infarction area is significantly reduced, and the heart function is significantly improved. The function of the IRF9 gene in coronary arteriosclerotic heart disease is mainly manifested by that the IRF9 gene can deteriorate coronary arteriosclerotic heart disease. As for the function of IRF9, the invention provides the application of the IRF9 in developing medicaments for treating coronary arteriosclerotic heart disease as a drug target, and the application of the IRF9 inhibitor in preparing medicaments for treating coronary arteriosclerotic heart disease.

Description

[0001] technical field [0002] The invention belongs to the field of gene function and application, in particular to the application of IRF9 (interferon regulatory factor 9) and its inhibitor in coronary atherosclerotic heart disease. [0003] Background technique [0004] Myocardial infarction (MI) is myocardial necrosis caused by acute and persistent coronary ischemia and hypoxia, and is a common type of ischemic heart disease. Cardiomyocytes will die due to ischemia, which is one of the common diseases that seriously threaten human health and life. How to intervene myocardial infarction caused by myocardial ischemia and protect the heart has been paid more and more attention. The most effective way to save myocardial infarction is to restore the blood flow of ischemic myocardium as soon as possible, that is, reperfusion. At present, intervention methods such as thrombolytic therapy, percutaneous transluminal coronary angioplasty, arterial bypass grafting, and cardiopu...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K48/00A61K39/395A61P9/10C12Q1/68
Inventor 李红良张晓东蒋丁胜张艳万埝刘小熊
Owner WUHAN UNIV
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