miR-423-5p参与AMI大鼠心肌细胞凋亡的机制研究

目的探讨miR-423-5p对急性心肌梗死(AMI)大鼠心肌细胞凋亡的影响及其机制。方法采用冠状动脉左前降支结扎法建立AMI大鼠模型,将其随机分为模型组、阴性组和干扰组,另设只开胸穿针不做冠状动脉结扎的假手术组,每组7只;采用Real-time PCR检测各组心肌组织中miR-423-5p的表达水平,心脏彩超检测各组大鼠的心脏功能,TCC法检测各组大鼠的心肌梗死面积,TUNEL法检测各组心肌细胞的凋亡指数,Western blot检测Cleaved caspase-3、Bax和Bcl-2蛋白的表达水平。结果与假手术组相比,模型组和阴性组中miR-423-5p表达水平、左室收缩末期内径(LVDS)、左室舒张末期内径(LVDD)和Bcl-2蛋白表达水平均降低,而左室长轴缩短分数(FS)、左室射血分数(LVEF)、心肌细胞凋亡指数、心肌梗死面积和Cleaved caspase-3、Bax蛋白表达水平均明显升高(P<0.05);与模型组和阴性组相比,干扰组中上述指标变化明显逆转(P<0.05)。结论 miR-423-5p可通过下调Cleaved caspase-3、Bax和上调Bcl-2表达抑制AMI大鼠心肌细胞凋亡,改善心脏功能,从而减轻AMI。

MiR-423-5p Participating in Apoptosis of Myocardial Cells in Rats with Acute Myocardial Infarction

Objective To investigate the effect of miR-423-5p on cardiomyocyte apoptosis in rats with acute myocardial infarction (AMI) and its mechanism. Methods The rat models of AMI were established by ligation of left anterior descending branch of coronary artery, and were randomly divided into model group, negative group and miR-423-5p group,meanwhile sham operation group was set up, in which only thoracotomy needle was used and no coronary artery ligation was performed,with 7 rats in each group.The expressions of miR-423-5p in myocardium of each group were Real-time PCR,cardiac function of rats in each group was measured by color doppler echocardiography,the myocardial infarction area was measured by TCC method, the apoptotic index of myocardial cells was measured by TUNEL method, and the expression levels of apoptotic related proteins Cleaved caspase-3, Bax and Bcl-2 were detected by Western blot. Results Compared with sham-operated group, the expression level of miR-423-5p, left ventricular end-systolic diameter (LVDS), left ventricular end-diastolic diameter (LVDD) and the expression level of Bcl-2 protein were decreased , while Left ventricular long axis shortening fraction (FS), left ventricular ejection fraction (LVEF), cardiomyocyte apoptosis index, myocardial infarction area and expression of Cleaved caspase-3 and Bax proteins were significantly increased in model group and negative group.Compared with the model group and the negative group, the changes of the above-mentioned indexes in the miR-423-5p group were significantly reversed ( P <0.05). Conclusion miR-423-5p can inhibit cardiomyocyte apoptosis and improve cardiac function through down-regulation of Cleaved caspase-3, Bax and up-regulation of Bcl-2 expression in AMI rats, thereby alleviating AMI.