miR-1调控Bcl-2/Bax介导的益气活血方抗心肌细胞凋亡研究

急性心梗后心肌缺血再灌注损伤（MIRI）病理基础为心肌细胞凋亡，微小RNA-1（miR-1）对心肌细胞凋亡具有负性调控作用；前期研究证实益气活血方具有抑制心梗后左室重构大鼠心肌细胞凋亡的作用，但机制不明。本项目利用大鼠MIRI模型和心肌细胞H9c2缺氧/复氧（H/R）模型，通过基因修饰方法对miR-1过表达和表达抑制来明确其与心肌细胞凋亡的相关性；通过研究MIRI及H/R后miR-1异常表达及其靶基因表达差异、测定心肌细胞线粒体膜功能状态以及钙信号变化等，探讨miR-1调控心肌细胞凋亡的分子机制；观察益气活血方预处理后MIRI及H/R条件下miR-1、Bcl-2/Bax、mPTP、Cyt C、caspase-3、Ca2+水平变化，探讨益气活血方在心肌细胞凋亡发生发展过程中的保护作用。本项目的完成将有助于阐明益气活血方抗心肌细胞凋亡的作用机制，为临床用药提供理论支持。

Myocardial cell apoptosis is the basic pathological process during myocardial ischemia reperfusion injury (MIRI) after acute myocardial infarction. It’s known that microRNA-1 (miR-1) has a negative regulatory effect on myocardial cell apoptosis, while the mechanism is not clear. Based on rat model of MIRI and H9c2 cell model of hypoxia/reoxygenation (H/R), the present project is trying to determine the correlation of cardiac apoptosis with overexpression of miR-1 or inhibition of its expression through genetic modification. We also explore the mechanism underlying cardiac apoptosis by measuring expression of miR-1 and its targeted genes, acquiring mitochondrial function, and conducting calcium signal. Finally, Yiqihuoxue Decoction is applied in advance to pre-treat MIRI rats and H/R cells, and the effects of Yiqihuoxue Decoction are conducted on the expression of miR-1, Bcl-2/Bax, mPTP, Cyt C, and caspase-3, as well as calcium signal, to investigate the protective effects of Yiqihuoxue Decoction on cardiac apoptosis. This project will help elucidate the mechanism of Yiqihuoxue Decoction against myocardial cell apoptosis and provide a theoretical basis for clinical medication.