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Application of mindin gene in the treatment of atherosclerosis

A technology of atherosclerosis and genes, which is applied in the field of gene function and application, can solve the unexplained problems of biological functions and possible mechanisms of action, and achieve the effect of promoting atherosclerosis

Active Publication Date: 2016-09-14
武汉惠康基因科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Our previous studies have shown that Mindin plays an important role in models of cardiac hypertrophy, stroke, and diabetes: in models of cardiac hypertrophy, Mindin, as an endogenous protective factor, inhibits maladaptive effects by inhibiting the AKT / GSK3β signaling pathway. Heart failure caused by cardiac remodeling (Bian ZY etl, Disruption of mindin exacerbates cardiac hypertrophy and fibrosis. J Mol Med (Berl) (2012); 90(8):895-910); in ischemic brain injury Mindin exerts biological functions through the Akt signaling pathway (Wang L etl, Mindin is a critical mediator of ischemic brain injury inan experimental stroke model. Exp Neurol (2013); 247:506-16); PPARα function, thereby regulating liver lipid metabolism in mice and reducing hepatic steatosis, obesity, inflammation, etc. (Zhu LH et al, Mindin / Spondin 2 inhibits hepatic steatosis, insulin resistance, and obesity via interaction with peroxisome proliferator-activated receptor α in mice. J Hepatol (2014); 60(5):1046-54); based on the above research, we believe that Mindin may play an important role in the early characteristic pathophysiological process of atherosclerosis, but its The biological function and possible mechanism of action in the early characteristic pathophysiological process of atherosclerosis have not been elucidated

Method used

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  • Application of mindin gene in the treatment of atherosclerosis
  • Application of mindin gene in the treatment of atherosclerosis
  • Application of mindin gene in the treatment of atherosclerosis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] Example 1 Mouse Atherosclerosis Model (AS) Obtained

[0038] 1. Grouping of experimental animals: male ApoE- / - mice and Mindin- / -ApoE- / - mice aged 8 weeks, weighing 19-25g, were fed with high-fat diet (Western Diets, HFD) respectively, ApoE - / - HFD group and Mindin- / -ApoE- / - HFD group consisted of 2 groups, with 20 rats in each group.

[0039] 2. Atherosclerosis model induced by high-fat diet:

[0040] ApoE- / - mice and Mindin - / -ApoE- / - mice were used to establish AS models, and phenotype correlation analysis was performed to clarify the role of Mindin gene in atherosclerotic diseases. From the age of 8 weeks, the mice in the HFD group were fed with high-fat diet for 28 weeks and sacrificed, and the samples were collected.

Embodiment 2

[0041] Example 2 Determination of plaque area in AS model mice

[0042] 1. Final mouse tissue harvesting

[0043] 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

[0056] Example 3 Determination of Plaque Stability in AS Model Mice

[0057] 1. Determination of collagen content in aortic sinus:

[0058]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, stained in a wet box for 90 minutes → remove the residue → 0.01N hydrochloric acid for 4 seconds → 70% alcohol once → 90% alcohol once → 100% alcohol 30s, 3 times → 2min in xylene, 3 times → cover the slide immediately while the xylene is still wet, and take pictures under the microscope.

[0059] Collagen ratio (%)=collagen area / plaque area*100%.

[0060] 2. Expression Determination of Aortic Sinus Macrophages and Smooth Muscle Cells

[0061] The ex...

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Abstract

The invention discloses a function and an application of a Mindin gene in treatment of atherosclerosis and belongs to the field of functions and applications of genes. In the invention, an ApoE - / - mouse and a Mindin - / - 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, a Mindin gene defect can significantly reduce a plague area in aorta, enhance stability of aortic sinus plagues and significantly alleviate an inflammatory response, which indicate that the Mindin, in the atherosclerosis, mainly has an effect of promoting formation of a plague in the aorta and especially promoting the atherosclerosis. On the basis of the functions hereinabove of the Mindin, the Mindin, as a drug target, can be used for screening a drug for preventing, alleviating and / or treating the atherosclerosis. An inhibitor of the Mindin 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 Mindin in the treatment of atherosclerosis, specifically the application of Mindin in the preparation of drugs for preventing, alleviating and / or treating atherosclerosis. 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] Athe...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K49/00A61K48/00A61K45/00A61K39/395A61P9/10
CPCY02A50/30
Inventor 李红良朱丽华张鹏程文林
Owner 武汉惠康基因科技有限公司
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