稳心颗粒干预PKC-SRF-miR-1通路调控Cx45/Cx43平衡抑制AMI后心律失常的研究

项目名称： 稳心颗粒干预PKC-SRF-miR-1通路调控Cx45/Cx43平衡抑制AMI后心律失常的研究

项目编号： No.81202685

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学八处

项目作者： 吴爱明

作者单位： 北京中医药大学

项目金额： 23万元

中文摘要： 急性心肌梗死(AMI)患者具有潜在性致死性心律失常发生的风险。研究证实缝隙连接蛋白43和45 (Cx43和Cx45)都与心律失常发病密切相关。但是AMI后Cx45/Cx43平衡如何变化？与心律失常发病的关系如何？分子调控机制是什么？这些问题尚不完全清楚。益气活血中药稳心颗粒抗心律失常疗效确切，文献和前期工作提示稳心颗粒除已知的多离子通道阻滞作用外，还可能具有缝隙连接保护作用。本项目制作大鼠AMI模型和心肌细胞缺氧损伤模型，以Cx45/Cx43的比例、分布和磷酸化水平的改变为指征，观察Cx45/Cx43失衡与AMI后心律失常发病的关系；以蛋白激酶C(PKC)为中心，研究PKC-SRF-miR-1通路调控Cx45/Cx43平衡的信号转导过程。从缝隙连接重构及其上游信号转导和小RNA调控角度，揭示稳心颗粒干预PKC-SRF-miR-1通路调控Cx45/Cx43平衡抑制AMI后心律失常的作用机制。

中文关键词： 缝隙连接重构；信号转导调控；心律失常；急性心肌梗死；稳心颗粒

英文摘要： Acute myocardial infarction (AMI) patients have potentially lethal arrhythmia risk. Studies confirmed that both connexin 43 and connexin 45 (Cx43 and Cx45) are closely related to the arrhythmia onset. But the Cx45/Cx43 balance how to change after AMI? Relationship with the arrhythmia onset? What is the molecular mechanism controlling? These issues are still unclear partly. Wenxinkeli, a traditional Chinese medicine of Yiqihuoxue, exactly have antiarrhythmic efficacy. Literatures and previous works have indicated that Wenxinkeli not only have the known ion channel blocking effect, but also may have a gap junction protective effect. This study produces a model of AMI in rats and myocardial hypoxia injury model, and regards the changes of the Cx45/Cx43 proportion, distribution and phosphorylation levels as indications to observe the relationship between the Cx45/Cx43 imbalance and the arrhythmia onset after AMI, and with protein kinase C ( PKC ) as the center to research the signal transduction process of PKC-SRF-miR-1 pathway in regulation of Cx45/Cx43 balance. From the gap junction remodeling and its upstream signal transduction and regulation of miRNA angle, to reveal the mechanism of arrhythmia suppression of Wenxinkeli by regulation of Cx45/Cx43 balance through intervention of PKC-SRF-miR-1 pathway after AMI.

英文关键词： gap junction remodeling；signal transduction controlling；arrhythmia；acute myocardial infarction；Wenxinkeli