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微小RNA-145-5p通过靶向ROCK1抑制缺氧/复氧诱导的H9c2心肌细胞凋亡。

MicroRNA-145-5p inhibits hypoxia/reoxygenation-induced apoptosis in H9c2 cardiomyocytes by targeting ROCK1.

作者信息

Cheng Chao, Xu Dong-Ling, Liu Xiao-Bo, Bi Shao-Jie, Zhang Juan

机构信息

Department of Cardiology, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250033, P.R. China.

Shandong Blood Center, Jinan, Shandong 250012, P.R. China.

出版信息

Exp Ther Med. 2021 Aug;22(2):796. doi: 10.3892/etm.2021.10228. Epub 2021 May 25.

Abstract

There is increasing evidence that microRNAs (miRs) play critical roles in the pathological and physiological processes associated with myocardial ischemia reperfusion (I/R). miR-145 has been extensively studied in the cardiovascular system; however, the role of miR-145 in myocardial I/R remains unclear. Therefore, the present study aimed to investigate the role and mechanism of miR-145-5p in myocardial I/R by establishing a hypoxia/reoxygenation (H/R) model using H9c2 cardiomyocytes. The expression of miR-145-5p was regulated by transfection and the potential target of miR-145-5p was identified. In addition, apoptosis of the cardiomyocytes was evaluated using flow cytometry and the detection of cleaved caspase-3 by western blotting. The results revealed that miR-145-5p expression was decreased while cell apoptosis and Rho-associated coiled-coil-containing kinase 1 (ROCK1) expression were increased in H/R-stimulated H9c2 cardiomyocytes. The upregulation of miR-145-5p reduced apoptosis and the expression of ROCK1 in H/R-stimulated H9c2 cardiomyocytes. Furthermore, the overexpression of ROCK1 significantly attenuated the miR-145-5p-induced reduction of apoptosis following H/R. In conclusion, the present study indicates that the overexpression of miR-145-5p inhibits H/R-induced cardiomyocyte apoptosis by targeting ROCK1.

摘要

越来越多的证据表明,微小RNA(miR)在与心肌缺血再灌注(I/R)相关的病理和生理过程中发挥着关键作用。miR-145已在心血管系统中得到广泛研究;然而,miR-145在心肌I/R中的作用仍不清楚。因此,本研究旨在通过使用H9c2心肌细胞建立缺氧/复氧(H/R)模型,探讨miR-145-5p在心肌I/R中的作用及机制。通过转染调节miR-145-5p的表达,并鉴定miR-145-5p的潜在靶标。此外,使用流式细胞术评估心肌细胞的凋亡,并通过蛋白质印迹法检测裂解的半胱天冬酶-3。结果显示,在H/R刺激的H9c2心肌细胞中,miR-145-5p表达降低,而细胞凋亡和含Rho相关卷曲螺旋的蛋白激酶1(ROCK1)表达增加。miR-145-5p的上调减少了H/R刺激的H9c2心肌细胞中的凋亡和ROCK1的表达。此外,ROCK1的过表达显著减弱了miR-145-5p诱导的H/R后凋亡减少。总之,本研究表明,miR-145-5p的过表达通过靶向ROCK1抑制H/R诱导的心肌细胞凋亡。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/704b/8170661/f558db4a3c8f/etm-22-02-10228-g00.jpg

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