circARHGAP10调控ANGPTL4表达对心肌缺血再灌注损伤的分子机制研究

心肌缺血再灌注损伤是围术期心血管事件的主要原因之一，但具体机制尚不清楚。环状RNA在心肌表达丰富，研究表明环状RNA参与了心肌缺血再灌注损伤。我们预实验发现：circARHGAP10在缺血再灌注心肌组织表达增加，与ANGPTL4表达正相关；抑制circARHGAP10表达，细胞缺氧复氧损伤减轻。进一步生信分析发现，circARHGAP10可能通过AGO2与miR-124-3p结合。据此，我们提出假说：circARHGAP10可能通过竞争结合miR-124-3p调控ANGPTL4表达，参与心肌缺血再灌注损伤。本研究拟通过细胞和动物模型，利用Luciferase、RIP、RNA Pulldown、FISH等技术，通过干扰和过表达目标基因，从分子、细胞和整体深入探讨circARHGAP10/miR-124-3p/ANGPTL4轴对心肌缺血再灌注损伤的调控机制，为围术期心肌保护提供新的理论依据。

Myocardial ischemia/reperfusion injury is one of the leading causes of perioperative cardiovascular events, but the specific mechanism is still unclear. Circular RNAs are abundantly expressed in myocardium. Studies have shown that circular RNAs are involved in myocardial ischemia/reperfusion injury. Our preliminary experiments found that the increased expression of circARHGAP10 in the ischemia/reperfusion myocardial tissues was positively correlated with the expression of ANGPTL4. In addition, inhibition of circARHGAP10 reduced hypoxia/reoxygenation injury in cardiomyocytes. Based on bioinformatic analysis, circARHGAP10 may bind to miR-124-3p through AGO2. Therefore, we hypothesize that circARHGAP10 may regulate ANGPTL4 expression through competing combination with miR-124-3p in myocardial ischemia/reperfusion injury. This study aims to explore the regulatory mechanisms of circARHGAP10/miR-124-3p/ANGPTL4 axis during myocardial ischemia/reperfusion injury by knockdown and overexpression of target genes with the use of Luciferase, RIP, RNA Pulldown, FISH and other technologies in cellular and animal models, which will provide a new theoretical basis for perioperative cardioprotection.