微小RNA-433在运动改善心肌梗死后心室重构中的作用和机制

心肌梗死是人类致死致残率极高的重大疾病之一，即使得到及时救治，心肌梗死后的心室重构同样严重影响患者的生存质量。目前临床上尚无针对心肌梗死后心室重构的特效治疗策略。运动康复发现有利于心肌梗死后心室重构，但其分子机制尚不清楚。我们的前期工作发现，运动能改善心肌梗死后心室重构。利用微小RNA芯片和荧光定量PCR技术发现，微小RNA-433在心肌梗死28天后的心脏中显著下调，且这一现象可被运动所逆转，增加微小RNA-433可减轻心肌细胞系缺氧复氧所致凋亡和坏死，提示该微小RNA433可能是运动防治心肌梗死后心室重构的关键分子。在此基础上，我们将进一步应用药物干预和转基因模式动物，结合分子、细胞及动物整体层面的研究，开展功能获得性和缺失性实验，从多层面多角度深入探讨微小RNA-433对心肌梗死后心室重构的防治效应及其分子基础，为心肌梗死后心室重构的治疗提供新的可能方案。

Myocardial infarction (MI) is a serious disease worldwide. Even with an early reperfusion therapy, the patients will still suffer from cardiac remodeling post-infarction, which also seriously affected the quality of life. Unfortunately, no therapy in the clinic can cure the remodeling post-MI. Exercise training has been widely used to benefit the patients after MI, however, the molecular mechanism is unclear. MicroRNAs (miRNAs, miRs) regulate cardiac physiological and pathological processes. Our preliminary data have demonstrated that exercise protected cardiac remodeling post-MI. Moreover, based on miRNA arrays and quantitative reverse transcriptase-polymerase chain reactions, we found that miR-433 was significantly down-regulated in AMI mouse than that of control mouse, and it could be restored by exercise. In addition, elevated miR-433 can protect apoptosis and necrosis caused by anoxia/reoxygention. Based on these results, we will firstly identify the role of miR-433 in the protective effects of exercise in cardiac remodeling post-MI. Secondly, we will investigate the potential target gene of miR-433 responsible for the protective effects by gene array, bioinformatic analysis, and the rescue experiments both in vitro and in vivo. Our project will identify a miRNA mediating the protective role of exercise in cardiac remodeling post-MI and will provide a novel therapeutic strategy for the treatment of ventricular remodeling post-MI.