SH2B3衔接蛋白对心肌梗死后心室重构的作用及其机制的研究

项目名称： SH2B3衔接蛋白对心肌梗死后心室重构的作用及其机制的研究

项目编号： No.81470400

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 马根山

作者单位： 东南大学

项目金额： 73万元

中文摘要： 心肌梗死后的心室重构是一个复杂的多因素参与调节的过程，免疫炎症反应在其中发挥着关键性作用，SH2B3是表达在T/B淋巴细胞、巨噬细胞上的衔接蛋白，并负性调控这些免疫细胞。我们的前期研究发现，SH2B3基因敲除后，小鼠心梗面积减小，心梗后的心肌肥厚、纤维化程度降低，生存率明显提高。但SH2B3在心肌梗死后心室重构中的作用国内外尚未见报道。本项目通过研究SH2B3对心肌细胞凋亡、炎症因子以及对巨噬细胞、T/B淋巴细胞等免疫细胞生物学特性的影响，探讨SH2B3对心肌梗死后心室重构的作用机制，并利用SH2B3基因敲除和心脏特异性转基因小鼠在体研究SH2B3对心肌梗死后心室重构的影响，系统阐明SH2B3对心肌梗死后心室重构的作用以及可能的分子机制，为防治心肌梗死后心室重构提供新的治疗靶点，为进一步研究新的治疗策略提供理论依据。

中文关键词： 急性心肌梗死；心室重构；免疫；SH2B3

英文摘要： Left ventricular remodeling after myocardial infarction is a complex process involving multiple factors, in which immune inflammatory response plays a key role.SH2B3 is a kind of adaptor protein which expressed in T/B lymphocytes、 macrophages, and acts as a negative regulator of these immune cells.In our previous study，we have found that the myocardial infarction area of SH2B3-knockout mouse is smaller than WT mouse, the degree of cardiac hypertrophy and fibrosis after myocardial infarction is also reduced.The survival rate of SH2B3-knockout mouse is obviously improved. So we suspect that，SH2B3 may play a very important role in the ventricular remodeling after myocardial infarction. In vitro, firstly，we primary culture myocardial cells of SH2B3-knockout and SH2B3-transgenic mice, studying the role of SH2B3 in inflammation and apoptosis, and exploring the mechanisms. Secondly，we study the role of SH2B3 in the biological characteristics of the macrophage and T/B lymphocyte immune cells. In vivo, we use SH2B3-knockout and SH2B3-transgenic mice to build the model of acute myocardial infarction, studying the impact of SH2B3 on ventricular remodeling after myocardial infarction. What we do in this project will provide a new therapeutic target and provide theoretical basis for the new treatment strategies.

英文关键词： acute myocardial infarction;ventricular remodeling;immune;SH2B3