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Function and application of MAPK (mitogen-activated protein kinase) signal-integrating kinase 2 in treatment of atherosclerosis

A technology of atherosclerosis and RNA interference, applied in the field of gene function and application, can solve problems such as unsatisfactory treatment and control effects, and achieve the effect of promoting atherosclerosis

Active Publication Date: 2014-12-24
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

The occurrence of atherosclerosis is the result of the joint action of multiple factors. There are many risk factors for atherosclerosis that have been discovered so far, but the relevant targeted treatment and control effects are not ideal. Lipid lowering and anti-inflammatory treatment are currently the most important treatments measure

Method used

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  • Function and application of MAPK (mitogen-activated protein kinase) signal-integrating kinase 2 in treatment of atherosclerosis
  • Function and application of MAPK (mitogen-activated protein kinase) signal-integrating kinase 2 in treatment of atherosclerosis
  • Function and application of MAPK (mitogen-activated protein kinase) signal-integrating kinase 2 in treatment of atherosclerosis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0046] Example 1 Mouse Atherosclerosis Model (AS) Obtained

[0047] 1. Grouping of experimental animals: 8 weeks old, weighing 19-25g, male, ApoE - / - Mice and Mnk2 - / - ApoE - / - Mice were fed high-fat diet (Western Diets, HFD) and low-fat diet (Normal chow, NC) respectively, ApoE - / - HFD group, ApoE - / - NC group, Mnk2 - / - ApoE - / - HFD group, Mnk2 - / - ApoE - / - The NC group consisted of 4 groups with 20 rats in each group.

[0048] 2. Atherosclerosis model induced by high-fat diet:

[0049] Using ApoE - / - Mice and Mnk2 - / - ApoE - / - In mice, AS models were established, and phenotype correlation analysis was performed to clarify the role of Mnk2 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

[0050] Example 2 Determination of plaque area in AS model mice

[0051] 1. Final mouse tissue harvesting

[0052] 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

[0067] Example 3 Determination of Plaque Stability in AS Model Mice

[0068] 1. Area Size Determination of the Center of Aortic Sinus Necrosis

[0069] Hematoxylin and eosin staining (HE staining) of the paraffin white slices of the aortic sinus was performed in the same manner as in Example 2.4, and the tissues containing cholesterol crystals and fiber structures without nuclei were selected and photographed under a microscope.

[0070] 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.

[0071] 2. Determination of collagen content in aortic sinus:

[0072] Sirius red (PSR) staining, the main steps are: take aortic sinus paraffin white slices and 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 1min→mass fraction 0.2% pho...

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Abstract

The invention discloses a function and application of an MAPK (mitogen-activated protein kinase) signal-integrating kinase 2 (Mnk2) in treatment of the atherosclerosis and belongs to the field of a function and application of a gene. According to the invention, an ApoE<- / -> mouse and an Mnk2<- / ->ApoE<- / -> mouse are used as experimental objects and an atherosclerosis module is obtained by high fat diet induction; the result shows that compared with the ApoE<- / -> mouse, the gene defect of the Mnk2 obviously reduces the plaque area of an aorta, reinforces stability of an aortic sinus plaque and obviously reduces the inflammatory response. The invention shows that the function of the Mnk2 in the atherosclerosis mainly represents promotion for forming of the aortic plaque and particularly promotion for the atherosclerosis. Aiming at the function of the Mnk2, the Mnk2 can be used as a drug target for screening a medicament for preventing, relieving and / or treating the atherosclerosis and an inhibitor of the Mnk2 can be used for preparing the medicament for preventing, relieving and / or treating the atherosclerosis.

Description

[0001] technical field [0002] The invention belongs to the field of gene function and application, and specifically relates to the function and application of a MAPK signal integration kinase 2 (Mnk2) in the treatment of atherosclerosis, in particular to the preparation of Mnk2 in the prevention, alleviation and / or treatment of atherosclerosis application in medicines. Background technique [0003] 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 caus...

Claims

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Application Information

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IPC IPC(8): C12Q1/02A61K49/00A61K45/00A61K48/00A61K39/395A61P9/10
Inventor 李红良王朗程文林张鹏
Owner 武汉惠康基因科技有限公司
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