辛伐他汀通过调控microRNA保护体外循环心脏手术心肌的研究

We had demonstrated that simvastatin can protect myocardium in cardiac surgery. microRNA(miRNA) played an important role in myocardial ischemic-reperfusion injury. But it is unclear whether simvastatin can protect myocardium in cardiac surgery by regulating miRNA. Our preliminary data showed that the expression of miRNA in the patients treated with simvastatin pre-operatively was significantly different from those patients without simvastatin therapy. We hypothesis that simvastatin may protect myocardium in cardiac surgery by regulating miRNA. In the project, we set up a cardiopulmonary bypass model in rats, and the different miRNA expression, target gene, inflammatory factor, and protein alteration will be detected by miRNA array, qRT-PCR and westernblot. Finally, rats will be treated with selected miRNA expressed differently, and the inflammatory factor and protein alteration will be measured. The aim of the study is to obtain the reliable evidence that simvastatin can protect myocardium in cardiac surgery by regulating miRNA, and to illuminate the new mechanism that simvastatin can protect myocardium in cardiac surgery. The finding will provide the scientific evidence of a new target of myocardial protection by simvastatin-regulated miRNA.

我们已证明辛伐他汀在体外循环心脏手术患者中有明确的心肌保护作用。 MicroRNA(miRNA)在心肌缺血再灌注损伤中发挥重要作用，但辛伐他汀是否通过调控miRNA来发挥心肌保护作用仍未清楚。我们预实验结果提示围手术期使用辛伐他汀的患者在心肌组织中miRNA表达水平有明显差异，由此我们提出辛伐他汀可能通过调控miRNA来发挥其在体外循环心脏手术中的心肌保护作用。本项目通过建立大鼠体外循环模型，利用miRNA array、qRT-PCR检测辛伐他汀处理病人和大鼠心肌组织中miRNA的改变、确立差异明确的miRNA和相应的靶基因及炎症介质和蛋白变化，再用这些差异表达的miRNA处理大鼠，检测相应的炎症介质和蛋白变化。旨在获得辛伐他汀通过调控miRNA保护体外循环心肌的可靠依据，阐明辛伐他汀对体外循环心脏手术心肌保护的新机制，为将来确立它调控的miRNA作为心肌保护的新靶点提供科学依据。

本项目前期研究证实了他汀类药物对非冠心病患者行体外循环心脏手术有心肌保护作用，而且证实他汀类药物可通过调控microRNA变化来影响心血管病理生理过程，本项目通过建立大鼠体外循环和心脏停跳模型，利用microRNA array、qRT-PCR检测辛伐他汀处理病人和大鼠心肌组织中microRNA的改变，试验结果显示，辛伐他汀可以通过调控miR-15a-5p抑制体外循环心脏手术中的心肌细胞凋亡，从而达到保护心肌的目的，试验结果阐明了辛伐他汀对体外循环心脏手术心肌保护的新机制，为将来确立辛伐他汀调控的microRNA作为心肌保护的新靶点提供科学依据。