Function and application of SH2B adapter protein 3(SH2B3) for treating cardiac hypertrophy

A technology of SH2B3, 1.SH2B3 is applied in the field of gene function and application to achieve the effect of worsening cardiac function and promoting cardiac hypertrophy

Active Publication Date: 2014-10-22
武汉惠康达科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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  • Function and application of SH2B adapter protein 3(SH2B3) for treating cardiac hypertrophy
  • Function and application of SH2B adapter protein 3(SH2B3) for treating cardiac hypertrophy
  • Function and application of SH2B adapter protein 3(SH2B3) for treating cardiac hypertrophy

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0052] Example 1 Expression of SH2B3 in the hearts of normal people and patients with cardiomyopathy

[0053]Normal human hearts (individuals who died from non-cardiac causes), hearts from patients with dilated cardiomyopathy (recipients undergoing heart transplantation, DCM) and hearts from patients with hypertrophic cardiomyopathy (recipients undergoing heart transplantation) were selected. SDS-PAGE-Western blotting test (Western blot) for proteins extracted from the heart, combined with antibodies that specifically recognize SH2B3 protein and cardiomyocyte hypertrophy markers ANP (Millipore, AB2232) and Myh7 (santa cruz, sc53090) Detection was performed to measure the expression of SH2B3 (santa cruz, sc7222), and β-Tubulin (Cell Signaling Technology, 2128) was used as an internal reference. Test results such as figure 1 , figure 2 As shown, the expressions of cardiomyocyte hypertrophy markers ANP and Myh7 were significantly up-regulated in the hearts of patients with dil...

Embodiment 2

[0054] Example 2 Expression of SH2B3 in wild-type mouse Sham group and AB operation 4W, 8W hearts

[0055] 1. The myocardial hypertrophy model adopts aortic arch constriction surgery, and the operation process of the model is as follows:

[0056] 1.1 Preoperative preparation

[0057] (1) Anesthesia: First weigh the mice, calculate the required amount of anesthetic (3% pentobarbital sodium) according to 90 mg / kg body weight, inject intraperitoneally, and record the injection time point. There is no obvious reaction between tail and toe pinching and the mouse is in good condition. This is the standard for successful anesthesia (generally there is no obvious reaction about 10 minutes after injection, and the mouse has a reaction to pinch toe about 50 minutes after anesthesia, and about 30 minutes after anesthesia is the best operation time).

[0058] (2) Preparation of the operation area: the skin of the left chest, left chest and armpit of the left forelimb of the mouse was rem...

Embodiment 3

[0067] Example 3 Detection of cardiac hypertrophy and fibrosis in mouse cardiac hypertrophy (AB) model

[0068] 1. The myocardial hypertrophy model adopts aortic arch constriction surgery, and the operation process of the model is as follows:

[0069] Wild-type mice, SH2B3 knockout mice, heart-specific SH2B3 transgenic mice and non-transgenic mice aged 8-10 weeks and weighing 23.5-27.5 g were selected and divided into sham operation group and cardiac hypertrophy model group. Group 10 mice. The modeling method is the same as in Example 2.

[0070] 2. Collect materials

[0071] (1) Preliminary work: prepare in advance a urine cup filled with 20mL of 10% formaldehyde by volume, and label it (mouse number, group, type of operation and date of collection). A petri dish filled with 10% KCl solution was placed at the sampling site. Turn on the analytical balance and set it to zero for later use. Mice were then weighed and sacrificed.

[0072] (2) Material collection: Ophthalmic...

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Abstract

The invention discloses a function and application of SH2B adapter protein 3(SH2B3) for treating cardiac hypertrophy. By virtue of the SH2B adapter protein 3(SH2B3), interrelation between the expression of SH2B3 gene and cardiac hypertrophy is determined; when the cardiac hypertrophy occurs, the expression of SH2B3 is obviously increased; activation of an Akt signal channel is suppressed by SH2B3 gene defect, the cardiac hypertrophy and fibrosis are also suppressed, and the heart function is protected; the activation of the Akt signal channel is remarkably accelerated by over expression of the SH2B3 gene, the cardiac hypertrophy and fibrosis are improved, and the heart function is deteriorated. Therefore, the SH2B3 gene can be used as a medicine target mark for screening medicines for protecting the heart function and/or preventing, relieving and/or treating the cardiac hypertrophy; the SH2B3 gene can be used as a target gene in gene treatment for designing and preparing medicines and/or biological reagents for protecting the heart function and/or preventing, relieving and/or treating the cardiac hypertrophy, so that an effective novel way is provided for the treatment of the cardiac hypertrophy.

Description

technical field [0001] The invention belongs to the field of gene function and application, and particularly relates to the function and application of SH2B adapter protein 3 (SH2B3) in the treatment of cardiac hypertrophy, specifically the application in the preparation of drugs for preventing, alleviating and / or treating myocardial hypertrophy. Background technique [0002] Cardiovascular system disease is one of the number one killers in the world at present, and the incidence rate of cardiovascular system disease in our country has increased to the first place of various major diseases at present. Studies have shown that myocardial hypertrophy is a common pathophysiological process of various cardiovascular diseases such as coronary heart disease, hypertension, arrhythmia, valvular heart disease, and cardiomyopathy, and is an independent risk factor for various cardiovascular complications. Myocardial hypertrophy refers to the increase in heart weight and volume in order...

Claims

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Application Information

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IPC IPC(8): A61K45/00A61K48/00A61K39/395A61P9/04
Inventor 李红良蒋丁胜蒋曦张晓东
Owner 武汉惠康达科技有限公司
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