miR-29调控ACE2对大鼠心肌缺血再灌注损伤的作用及机制研究

Reperfusion is the most effective treatment to save impending myocardial necrosis resuled from ischemic by thrombolysis or percutaneous coronary intervention, however, it causes subsequent myocardial ischemia-reperfusion injury. Our preliminary research work found that angiotensin-converting enzyme 2 (ACE2) played an important role in myocardial ischemia-reperfusion injury that was exacerbated with down-regulation of ACE2. Recently, various studies demonstrated that many microRNAs were associated with the process of myocardial ischemia-reperfusion injury by regulating the target genes. We predicted the expression of ACE2 was mediated by microRNA-29 in myocardial ischemia-reperfusion injury. Moreover, evidence indicated that the microRNA-29 expression was down-regulated in myocardial ischemia-reperfusion. The extent of injury could be attenuated with down-regulation of microRNA-29 expression. Thus, our research is mainly focused on 1) investigation of the pivotal effect of microRNA-29 on ACE2 expression in myocardial ischemia-reperfusion; 2) clarification of the GATA4 signal pathway with the regulation of microRNA-29 to ACE2. The purpose of this project is to provide a promising therapeutic strategy for myocardial ischemia-reperfusion injury.

再灌注治疗（如溶栓、经皮冠状动脉介入术等）是心肌缺血后挽救心肌坏死的最有效方法，然而它也会给心肌带来进一步损伤。我们前期研究发现血管紧张素转换酶2在心肌缺血再灌注损伤中起着重要作用，其表达下降会加重心肌损伤。最近研究表明多种microRNA通过调控目的基因的表达参与了心肌缺血再灌注损伤过程；我们应用TargetScan 工具预测发现调控血管紧张素转换酶2 mRNA表达的microRNA为microRNA-29，同时有研究表明心肌缺血再灌注时microRNA-29表达下降，下调microRNA-29能够减轻心肌缺血再灌注损伤。本项目主要内容为1）探讨microRNA-29是否是心肌缺血再灌注中调控血管紧张素转换酶2表达的关键microRNA；(2) GATA4信号通路是否与miR-29调控ACE2的表达有关；为防治心肌缺血再灌注损伤提供新的思路。