MicroRNA-497通过下调Mfn2促进心肌缺血再灌注损伤小鼠心肌细胞增殖并抑制心肌细胞凋亡
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MicroRNA-497 promotes proliferation and inhibits apoptosis of cardiomyocytes through the downregulation of Mfn2 in a mouse model of myocardial ischemia-reperfusion injury
背景与目的：心肌缺血再灌注（I/R）损伤影响全世界数百万人，死亡率很高。有研究发现 microRNA-497 (miR-497)与心肌细胞凋亡有关，本研究旨在探讨miR-497通过靶向作用于Mfn2对小鼠心肌缺血再灌注损伤的影响。
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方法：用BALB/c小鼠建立I/R模型，一部分小鼠在I/R前注射miR497激动剂，观察miR497是否能减轻I/R引起的损伤。利用生物信息学网站和双荧光素酶报告系统检测miR497和Mfn2基因之间的关系。然后，用不同的类似物、抑制剂和siRNA转染细胞，进一步探讨miR497对I/R的作用。采用Western blot分析法和逆转录-定量聚合酶链反应 (RT-qPCR)检测转染后心肌组织和心肌细胞中miR-497, Mfn2, Fas, Bcl-2, Bax and Caspase-3的表达。用CCK-8分析和流式细胞技术检测转染后各组心肌细胞增殖、细胞周期分布和凋亡情况。
结果：有心功能障碍的I/R小鼠在注射miR-497激动剂后，I/R损伤作用减轻。Mfn2被证实为miR497的靶基因。miR-497依次抑制Mfn2表达和心肌细胞凋亡。miR－497过表达和Mfn2基因沉默可促进离体小鼠心肌细胞增殖，miR－497过表达和Mfn2基因沉默也可促进小鼠心肌细胞进入细胞周期，并抑制离体培养的心肌细胞凋亡。
结论：本研究为miR497通过下调心肌缺血再灌注损伤小鼠模型中Mfn2表达而促进心肌细胞增殖和抑制心肌细胞凋亡提供了强有力的证据。
Qin L1, Yang W1, Wang YX1,et al.MicroRNA-497 promotes proliferation and inhibits apoptosis of cardiomyocytes through the downregulation of Mfn2 in a mouse model of myocardial ischemia-reperfusion injury[J].Biomed Pharmacother,2018.
Introduction: Myocardial ischemia-reperfusion (I/R) injury affects millions of people worldwide and has a veryhigh mortality rate. Since microRNA-497 (miR-497) has been found to be related with cardiomyocyte apoptosis,this study aimed to explore the effect of miR-497 by targeting Mfn2 in a mouse model of myocardial ischemiareperfusion (I/R) injury.
Materials: BALB/c mice were modeled with I/R and some were injected with miR-497 agomir before I/R to observe whether miR-497 alleviates the injury that occurs as a result of I/R. Bioinformatics website and dualluciferase reporter gene assay were employed in order to detect the relations between miR-497 and Mfn2 gene.Next, cells were extracted to be transfected with different mimic, inhibitor and siRNAs to further explore howmiR-497 acts to I/R. Western blot analysis and reverse transcription quantitative polymerase chain reaction (RTqPCR) were conducted to measure expressions of miR-497, Mfn2, Fas, Bcl-2, Bax and Caspase-3 in myocardial tissues and cardiomyocytes after transfection. CCK-8 assay and flow cytometry were used to determine proliferation, cell cycle distribution and apoptosis of cardiomyocytes in each group after transfection.
Results: Mice with I/R had myocardial dysfunction but before the injection with miR-497 agomir, the impairment was alleviated. Mfn2 was verified as the target gene of miR-497. The inhibition of miR-497 in turn inhibitsMfn2 expression and cardiomyocyte apoptosis. The overexpression of miR-497 and Mfn2 gene silencing canlead to the promotion of proliferation capability of mice cardiomyocytes in vitro. Overexpressed miR-497 and Mfn2 gene silencing can also facilitate cell cycle entry and inhibit the apoptosis cardiomyocytes of mice in vitro.
Conclusion: The present study provided strong evidence that miR-497 promotes proliferation and inhibits apoptosis of cardiomyocytes by downregulating the expression of Mfn2 in a mouse model of myocardial I/R injury.
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