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Function and application of MAPK (mitogen-activated protein kinase) signal-integrating kinase 1 in treatment of atherosclerosis

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

Inactive Publication Date: 2014-12-24
WUHAN UNIV
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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 1 in treatment of atherosclerosis
  • Function and application of MAPK (mitogen-activated protein kinase) signal-integrating kinase 1 in treatment of atherosclerosis
  • Function and application of MAPK (mitogen-activated protein kinase) signal-integrating kinase 1 in treatment of atherosclerosis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0045] Example 1 Obtaining a mouse atherosclerosis model (AS)

[0046] 1. Experimental animal grouping: select 8 weeks old, weight 19-25g, male, ApoE - / - Mice and Mnk1 - / - ApoE - / - Mice were fed with high-fat diet (Western Diets, HFD) and low-fat diet (Normal chow, NC), ApoE - / - HFD group, ApoE - / - NC group, Mnk1 - / - ApoE - / - HFD group, Mnk1 - / - ApoE - / - There are 4 groups in the NC group, with 20 animals in each group.

[0047] 2. The process of atherosclerosis model induced by high-fat feed:

[0048] Adopt ApoE - / - Mice and Mnk1 - / - ApoE - / - Mice, establish an AS model, perform phenotypic correlation analysis, and clarify the role of Mnk1 gene on atherosclerotic disease. Starting from 8 weeks of age, mice in the HFD group were sacrificed after being fed a full course of high-fat diet for 28 weeks and samples were collected. The NC group was sacrificed after being fed a full course of low-fat diet for 28 weeks and samples were collected.

Embodiment 2

[0049] Example 2 Measurement of plaque area in AS model mice

[0050] 1. Mouse terminal tissue collection

[0051] The mice were fed high-fat or low-fat feed until 28 weeks, weighed, and anesthetized the mice with 3% sodium pentobarbital, 90 mg / kg, fixed with a needle on the sample plate, and moistened the chest and abdomen skin of the mice with gauze. Ophthalmic scissors cut open the chest cavity, expose the heart, cut open the right atrial appendage, pierce the needle of the infusion set into the left ventricle, and slowly inject 10-15mL PBS buffer with a 50mL syringe. When the right atrial appendage is clear, replace it with 4% poly Continue to inject 10-15 mL of formaldehyde. After the perfusion, the organs in the thoracic and abdominal cavity were removed, leaving only the heart. Place the mouse under a microscope, separate the fascia and adipose tissue around the aortic arch, cut off the head and arm trunk, put it into a 5mL EP tube containing 4% paraformaldehyde, cut the h...

Embodiment 3

[0066] Example 3 Determination of plaque stability in AS model mice

[0067] 1. Determination of the area of ​​the center of aortic sinus necrosis

[0068] Hematoxylin-eosin staining (HE staining) of paraffin white slices of aortic sinuses, the method is the same as that in Example 2.4, and the tissues containing cholesterol crystals and no nuclear fiber structure are selected and photographed under a microscope.

[0069] Determination of the area of ​​the necrotic center: Use Image-Pro Plus 6.0 image analysis software to circle the area of ​​the necrotic center.

[0070] 2. Determination of collagen content in aortic sinus:

[0071] Sirius Red (PSR) staining, the main steps are: take aortic sinus paraffin white slices and bake at 55°C for 30 min → xylene for 2 min, 3 times → 100% alcohol for 1 min → 95% alcohol for 1 min → 70% alcohol for 1 min → running water for 10 min → Double distilled water for 1 min→mass fraction 0.2% phosphomolybdic acid for 2 min→0.1% Sirius scarlet picric aci...

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Abstract

The invention discloses a function and application of an MAPK (mitogen-activated protein kinase) signal-integrating kinase 1 (Mnk1) 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 Mnk1<- / ->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 Mnk1 obviously reduces the plaque area of an aorta tree, reinforces stability of an aortic sinus plaque and obviously reduces the inflammatory response. The invention shows that the function of the Mnk1 in the atherosclerosis mainly represents promotion for forming of the aortic plaque and particularly promotion of the atherosclerosis. Aiming at the function of the Mnk1, the Mnk1 can be used as a drug target for screening a medicament for preventing, relieving and / or treating the atherosclerosis and an inhibitor of the Mnk1 can be used for preparing the medicament for preventing, relieving and / or treating the atherosclerosis.

Description

[0001] Technical field [0002] The present invention belongs to the field of gene function and application, and specifically relates to the function and application of MAPK signal integration kinase 1 (Mnk1) in the treatment of atherosclerosis, in particular to the preparation of Mnk1 in the prevention, alleviation and / or treatment of atherosclerosis Application of the drug. Background technique [0003] Cardiovascular and cerebrovascular diseases are the main cause of death in many developed countries, and their incidence and mortality in my country are also increasing year by year. The basis of cardiovascular and cerebrovascular diseases is atherosclerosis (Atheosclersisis, AS). Atherosclerosis can make arterial walls thicken, harden, and narrow the lumen, leading to many cardiovascular and cerebrovascular events. The rupture of atherosclerotic unstable plaques, the aggregation of platelets, and the formation of thrombosis caused acute coronary artery stenosis and occlusion ar...

Claims

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Application Information

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IPC IPC(8): A61K45/00A61K48/00A61K39/395A61P9/10
Inventor 李红良张鹏黄玲张晓晶
Owner WUHAN UNIV
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