白藜芦醇保护缺血再灌注大鼠心肌作用与miR-21的相关性

Correlation Between miR-21 and the Protective Effects of Resveratrol Against Myocardial Ischemia/Reperfusion Injury in Rats

目的观察白藜芦醇预处理后大鼠心肌微小RNA(miRNA)的表达变化,分析白藜芦醇介导的心肌保护作用与miR-21之间有否关系。方法通过miRNA芯片微阵列方法和qRT-PCR检测并验证白藜芦醇灌胃预处理后的大鼠心肌miRNA表达谱;建立大鼠心肌缺血再灌注损伤模型,检测各组心肌梗死面积、心肌细胞凋亡率以及miR-21的表达水平。结果白藜芦醇预处理后,大鼠心肌的miR-21表达水平约为对照组的2.5倍;miR-21阻遏剂对白藜芦醇预处理引起的miR-21高表达产生了明显的抑制作用;过表达的miR-21显著降低了心肌细胞凋亡率,心肌组织梗死面积明显缩小。结论白藜芦醇可以调控心肌多种miRNA的表达水平,通过促进miR-21的表达,白藜芦醇能够抑制心肌细胞的凋亡,从而减轻缺血再灌注对心肌的损伤。

Aim To observe effects of resveratrol （Res） preconditioning on miRNA expression signature in rat hearts, and analyse the relationship between Res-mediated cardiac protection and miR-21. Methods The expression profiles of miRNAs in rat hearts after Res preconditioning were detected with a miRNAs microarray chip and the results were confirmed by qRT-PCR. After myocardial ischemia/reperfusion （I/R） injury model was established, myocardial infarct size, percent of myocardial apoptosis and expression of miR-21 were tested. Results miR-21 was one of the most up- regulated miRNAs in hearts by Res preconditioning and its expression was increased more than 2. 5 fold compared with the control. The up-regulation of miR-21 was significantly inhibited by antagomiR-21. Cardiac cell apoptosis and myocardial infarct size were significantly decreased by up-regulation of miR-21. Conclusion miRNA signature in rat hearts with Res preconditioning has revealed that multiple miRNAs are regulated by Res. Among them, Res has a protective effect on I/R by reducing cardiac cell apoptosis via miR-21.