Function and application of SH2B adapter protein 1 (SH2B1) in myocardial hypertrophy treatment

A 1. SH2B1, SH2B1 technology, applied in the field of gene function and application, can solve the problem of not fully explaining the mechanism of cardiac hypertrophy, and achieve the effect of worsening cardiac function and promoting cardiac hypertrophy

Active Publication Date: 2014-11-12
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

However, existing studies cannot fully explain the mechanism of cardiac hypertrophy

Method used

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  • Function and application of SH2B adapter protein 1 (SH2B1) in myocardial hypertrophy treatment
  • Function and application of SH2B adapter protein 1 (SH2B1) in myocardial hypertrophy treatment
  • Function and application of SH2B adapter protein 1 (SH2B1) in myocardial hypertrophy treatment

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0055] Example 1 Expression of SH2B1 in the hearts of normal people and patients with cardiomyopathy

[0056] 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. body, HCM), SDS-PAGE-Western blotting test (Western blot) was performed on the protein extracted from the heart, and the specific recognition SH2B1 (R&D, AF6915) protein and cardiomyocyte hypertrophy markers ANP (Millipore, AB2232), β-MHC ( Santa Cruz, sc53090) antibody was detected to measure the expression of SH2B1, and GAPDH (Cell Signaling Technology, 2118) was used as an internal reference. Test results such as figure 1 As shown, compared with normal human hearts, the expression of cardiomyocyte hypertrophy markers ANP and β-MHC in patients with cardiomyopathy was significantly up-...

Embodiment 2

[0057] Example 2 Expression of SH2B1 in wild-type mouse Sham group and AB operation 4W, 8W hearts

[0058] 1. The myocardial hypertrophy model adopts aortic arch constriction surgery, and the operation process of the model is as follows:

[0059] 1.1 Preoperative preparation

[0060] (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).

[0061] (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

[0070] Example 3 Effects of SH2B1 interference (Adsh SH2B1) and overexpression (Ad SH2B1) adenoviruses on the expression of SH2B1 in AngⅡ-stimulated primary cardiomyocytes

[0071] 1. Primary neonatal SD rat cardiomyocyte culture

[0072] (1) Eight newborn Sprague-Dawley suckling mice were sterilized with 75% alcohol below the neck, and the heart was removed with ophthalmic scissors and micro forceps, and placed in a glass plate filled with 10mL DMEM / F12 solution. Take another one and repeat the above process.

[0073] (2) Wash the heart with DMEM / F12 medium, and cut the heart into 1-2mm 3 fragments. Transfer to a serum bottle with a rotor, suck off DMEM / F12, and add trypsin digestion solution. Rotate at 120r / min, digest for 15min, rest for a few seconds, and discard the supernatant.

[0074] (3) Add trypsin digestion solution, the speed is 120r / min, and digest for 15min. Stand still for a few seconds, aspirate the supernatant, terminate the digestion with DMEM / F12 medium...

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Abstract

The invention discloses a function and application of SH2B adapter protein 1 (SH2B1) in myocardial hypertrophy treatment. According to the function and application, the mutual relation between SH2B1 genetic expression and myocardial hypertrophy is determined; the SH2B1 expression rises obviously when the myocardial hypertrophy happens; SH2B1 interference and overexpression adenovirus are used for restraining and promoting cardiomyocyte hypertrophy respectively; the SH2B1 gene defect and overexpression are used for restraining and obviously raising Jak2/Stat3 signal pathway activation respectively, so that cardiac hypertrophy and fibrosis are restrained and promoted, and the cardiac function can be protected and deteriorated. Hence, the SH2B1 gene can be used as a drug target to be used for screening drugs for protecting the cardiac function and/or preventing, relieving and treating cardiac hypertrophy; the SH2B1 gene can be used as a target gene in gene therapy to be used for designing and preparing the drugs for protecting the cardiac function and/or preventing, relieving and treating cardiac hypertrophy; a new path is provided for cardiac hypertrophy treatment.

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 1 (SH2B1) in the treatment of cardiac hypertrophy, specifically the application in the preparation of drugs for preventing, alleviating and / or treating cardiac hypertrophy. Background technique [0002] With economic development and improvement of living standards, heart failure accounts for an increasingly high proportion of cardiovascular events and mortality. It is the most common complication of myocardial It is a complex syndrome that satisfies the body's metabolic needs, and it is one of the main causes of death for humans today. The current study focuses on left ventricular hypertrophic remodeling of the heart, a currently recognized risk factor for cardiovascular mortality. Myocardial hypertrophy is an adaptive response of the heart to many external stimuli, such as hypertension, valvular heart d...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/68A61K45/00A61K48/00A61P9/00
CPCA61K31/7088A61K39/3955A61K45/00C12Q1/6883C12Q2600/136C12Q2600/158
Inventor 李红良蒋丁胜蒋曦张晓东
Owner 武汉惠康基因科技有限公司
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