Function and application of signal regulatory protein 1 treating atherosclerosis

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

Inactive Publication Date: 2015-03-04
WUHAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

It is speculated that SHPS1 may play an important role in the characteristic pathophysiological process of atherosclerosis, but its biologic

Method used

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  • Function and application of signal regulatory protein 1 treating atherosclerosis
  • Function and application of signal regulatory protein 1 treating atherosclerosis
  • Function and application of signal regulatory protein 1 treating atherosclerosis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0045] Example 1 Mouse Atherosclerosis Model (AS) Obtained

[0046] 1. Grouping of experimental animals: 8 weeks old, weighing 19-25g, male, ApoE - / - mice and SHPS1 - / - ApoE - / - Mice were fed high-fat diet (Western Diets, HFD) and low-fat diet (Normal chow, NC) respectively, ApoE - / - HFD group, ApoE - / - NC group, SHPS1 - / - ApoE - / - HFD group, SHPS1 - / - ApoE - / - The NC group consisted of 4 groups with 20 rats in each group.

[0047] 2. Atherosclerosis model induced by high-fat diet:

[0048] Using ApoE - / - mice and SHPS1 - / - ApoE - / - In mice, AS models were established, and phenotype correlation analysis was performed to clarify the role of SHPS1 gene on 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

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

[0050] 1. Final mouse tissue harvesting

[0051] 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

[0066] Example 3 Determination of Plaque Stability in AS Model Mice

[0067] 1. Area Size Determination of the Center of Aortic Sinus Necrosis

[0068] 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.

[0069] 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.

[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 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 function and application of signal regulatory protein 1 (SHPS1) treating atherosclerosis, and belongs to the field of functions and application of genes. According to the technical scheme, an ApoE<-/-> mouse and a SHPS1<-/->ApoE<-/-> mouse are taken as experiment objects, atherosclerotic models are obtained through high-fat diet induction, and results show that compared with the ApoE<-/-> mouse, SHPS1 gene defect leads to substantial reduction of the aorta plaque area, stability enhancement of aortic sinus plaque and mitigation of inflammation reaction. The results show that SHPS1 mainly has the effects of promoting formation of aorta plaque area and especially promoting atherosclerosis in the functions of atherosclerosis. Aiming at the above functions of SHPS1, SHPS1 can be used as a medicine target and is applied to screen medicines for preventing, alleviating and/or treating atherosclerosis, and an inhibitor of SHPS1 is applicable to prepare medicines for preventing, alleviating and/or treating 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 signal regulatory protein 1 (SHPS1) in the treatment of atherosclerosis. application in medicine. 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 causes of acute coronary syndrome (ACS). [0004] Atherosclerosis is a chronic inflammatory disease involving multip...

Claims

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Application Information

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IPC IPC(8): A61K49/00A61K48/00A61K39/395A61K45/00A61P9/10
Inventor 李红良张鹏程文林赵光年
Owner WUHAN UNIV
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