MicroRNA-155调控急性心肌梗死后室性心律失常的机制研究

室性心律失常（VAs）是急性心肌梗死（AMI）患者猝死的主要原因，其重要电生理机制为心肌细胞离子通道和转运体表达和功能异常。MicroRNA-155(miR-155)可直接调控细胞膜钠通道、钙通道和钙泵的基因表达，在AMI 后心室肌表达显著升高。我们的预实验研究显示，miR-155 基因敲除小鼠其心室肌L 型钙电流显著增大，动作电位时程明显延长，提示miR-155 可能对VAs 有重要调控作用，但目前尚无相关研究报道。有鉴于此，本项目拟运用miR-155 基因敲除小鼠和心脏特异性miR-155 过表达小鼠，通过在体、离体和细胞水平的电生理研究，结合分子生物学研究，对miR-155 在AMI 后急性期和慢性期VAs中的作用及其机制展开系统研究，力图明确miR-155 对AMI 后不同阶段VAs 的影响及其机制，为有效防治AMI 后VAs 提供实验室依据和新靶点。

Ventricular arrhythmias(VAs) are the main cause of sudden death in patients with acute myocardial infarction(AMI). The abnormality in the expression and function of cardiac myocyte ionic channels and transporters is the critical underlying electrophysiological mechanism of VAs. MicroRNA-155(miR-155) can direatly regulate plasma membrane sodium channel, calcium channel and calcium pump,which is increased in ventricular myocardium after AMI. Our preliminary experiment showed that ventricular L type calcium current was signifcantly increased and monophasic action potential duration was prolonged in miR-155 knockout mice, which imply that miR-155 may play an important role in the regulation of VAs. However, there is no any report about the effects and mechanisms of miR-155 on VAs after AMI so far. Therefore, in the present study, we will investigate the effects and mechanisms of miR-155 on VAs after AMI using in vivo and in vitro electrophysiological techniques, and molecular biology methods in transgenic mice with cardiac-specific overexpression of human miR-155 gene and miR-155 knockout mice. We aim to clarify the effects and mechanisms of miR-155 on VAs after AMI and provide experimental evidence and new molecular target for treatment and prevention of VAs after AMI.