微小RNA-145调控EPS15介导的细胞自噬参与心房颤动发生的机制  

Mechanism of microRNA-145 regulation of EPS15 mediated cellular autophagy involved in occurrence of atrial fibrillation

作　　者：王超 姜晨阳 俞虹宇 王如兴 钟国强[2] WANG Chao;JIANG Chenyang;YU Hongyu;WANG Ruxing;ZHONG Guoqiang(Department of Cardiology,the Affiliated Wuxi People’s Hospital of Nanjing Medical University,Wuxi Jiangsu 214023;Department of Cardiology,the First Hospital Affiliated to Guangxi Medical University,Nanning Guangxi 530021,China)

机构地区：[1]南京医科大学附属无锡人民医院心内科,江苏无锡214023 [2]广西医科大学附属第一医院心内科,广西南宁530021

出　　处：《实用心电与临床诊疗》2025年第1期29-35,共7页PRACTICAL ELECTROCARDIOLOGY AND CLINICAL TREATMENT

基　　金：国家自然科学基金资助项目(82370342);江苏省自然科学基金资助项目(BK20231145)。

摘　　要：目的探讨微小RNA(microRNA,miRNA)-145调控表皮生长因子受体底物15(epidermal growth factor receptor pathway substrate 15,EPS15)介导的细胞自噬参与心房颤动(简称房颤)发生的机制,寻找房颤发生过程中潜在的生物标志物,为房颤的预防和治疗提供新思路。方法收集58例风湿性心脏病换瓣手术患者的右心耳组织,将这些患者分为窦性心律组(16例)和房颤组(42例)。通过尾静脉注射Ach-CaCl 2混合溶液构建大鼠房颤模型,注射生理盐水作为窦性心律组。检测两组患者右心耳组织及两组大鼠心房中miRNA-145的表达水平,及其EPS15、Cx43、LC3、p62的RNA和蛋白表达水平。构建体外自噬模型,探讨miRNA-145靶向调控EPS15介导的细胞自噬参与房颤发生的机制。结果窦律组患者右心耳及窦律组大鼠心房miRNA-145、Cx43的RNA及蛋白相对表达量分别高于房颤组患者及房颤组大鼠(均P<0.05),而EPS15的RNA及蛋白相对表达量分别低于房颤组患者及房颤组大鼠(均P<0.05)。体外实验结果显示,miRNA-145能够通过EPS15调控H9c2细胞的自噬程度(P<0.05)。结论miRNA-145可通过调控EPS15介导的细胞自噬参与房颤的发生,表现为miRNA-145显著下调、EPS15上调、自噬增强和Cx43降解。Objective To investigate the mechanism of microRNA(miRNA)-145 regulation of EPS15 mediated cellular autophagy involved in the occurrence of atrial fibrillation(AF),and to find the potential biomarkers during the development of AF providing new ideas for the prevention and treatment of AF.Methods The right atrial appendage tissues were collected from 58 patients undergoing valve replacement surgery due to rheumatic heart disease.These patients were divided into sinus rhythm(SR)group(16 cases)and AF group(42 cases).The rat model of AF was constructed by tail vein injection of Ach-CaCl 2 mixture solution,while normal saline was injected as the SR group.We detected the expression levels of miRNA-145 in the right atrial appendage tissues of patients and the atrium of the rats in the two groups,as well as the RNA and protein expression levels of EPS15,Cx43,LC3 and p62.The in vitro autophagy model was established,in order to explore the mechanism of miRNA-145 targeted regulation of EPS15 mediated cellular autophagy involved in the occurrence of AF.Results The relative expression levels of RNA,and protein of miRNA-145 and Cx43 in the right atrial appendage of patients in the SR group and in the atrium of rats in the SR group were separately higher than those of patients in the AF group and rats in the AF group(all P<0.05),while the relative expression levels of RNA and protein of EPS15 were separately lower than those of patients in the AF group and rats in the AF group(all P<0.05).In vitro experiment results showed that miRNA-145 could regulate the degree of autophagy of H9c2 cells through EPS15(P<0.05).Conclusion MiRNA-145 participates in the occurrence of AF by regulating EPS15 mediated autophagy,which is manifested by significantly down-regulated miRNA-145,up-regulated EPS15,enhanced autophagy and degraded Cx43.

关 键 词：心房颤动 微小RNA-145 自噬 CX43 EPS15 P62 LC3 

分 类 号：R541.75[医药卫生—心血管疾病]