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miR-292-5p 通过过氧化物酶体增殖物激活受体-α/-γ 信号通路对心肌缺血再灌注损伤的影响。

Effects of microRNA-292-5p on myocardial ischemia-reperfusion injury through the peroxisome proliferator-activated receptor-α/-γ signaling pathway.

机构信息

Department of Cardiovascular Diseases, The Third People's Hospital of Yunnan Province, The Second Affiliated Hospital of Dali University, 650011, Kunming, People's Republic of China.

Pathogenic Organisms Department of Experimental Center, School of Basic Medical Sciences, Kunming Medical University, 650500, Kunming, People's Republic of China.

出版信息

Gene Ther. 2018 Jun;25(3):234-248. doi: 10.1038/s41434-018-0014-y. Epub 2018 Apr 18.

Abstract

Ischemia-reperfusion injury (IRI) is a major cause of cardiac damage following various pathological processes, such as free radical damage and cell apoptosis. This study aims to investigate whether microRNA-292-5p (miR-292-5p) protects against myocardial ischemia-reperfusion injury (IRI) via the peroxisome proliferator-activated receptor (PPAR)-α/-γ signaling pathway in myocardial IRI mice models. Mouse models of myocardial IRI were established. Adult male C57BL/6 mice were divided into different groups. The hemodynamic indexes, levels of related inflammatory factors and serum myocardial enzymes, and malondialdehyde (MDA) content and the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were detected. The 2,3,5-triphenyltetrazolium chloride (TTC) staining was applied to determine infarct size. TUNEL staining was used to detect cardiomyocyte apoptosis. RT-qPCR and western blotting were performed to measure the related gene expressions. Compared with the model group and the T0070907 + miR-292-5p inhibitor, the miR-292-5p inhibitor group exhibited decreased incidence and duration time of ventricular tachycardia and ventricular fibrillation, serum myocardial enzymes, TNF-α, IL-6, IL-1β, MDA, cardiomyocyte apoptosis, expressions of Bax and p53 in addition to increased SOD and GSH-Px activity, and increased expressions of Bcl-2, PPARα, PPARγ, PLIN5, AQP7, and PCK1. The T0070907 group exhibited opposite results compared to the miR-292-5p inhibitor group. The results indicate that miR-292-5p downregulation protects against myocardial IRI through activation of the PPAR-α/PPAR-γ signaling pathway.

摘要

缺血再灌注损伤(IRI)是多种病理过程(如自由基损伤和细胞凋亡)导致心脏损伤的主要原因。本研究旨在探讨微小 RNA-292-5p(miR-292-5p)是否通过过氧化物酶体增殖物激活受体(PPAR)-α/-γ 信号通路在心肌 IRI 小鼠模型中对心肌 IRI 起保护作用。建立了心肌 IRI 小鼠模型。雄性 C57BL/6 成年小鼠被分为不同的组。检测各组的血流动力学指标、相关炎症因子和血清心肌酶水平、丙二醛(MDA)含量和超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)的活性。采用 2,3,5-氯化三苯基四氮唑(TTC)染色法测定梗死面积。TUNEL 染色法检测心肌细胞凋亡。采用 RT-qPCR 和 Western blot 检测相关基因表达。与模型组和 T0070907+miR-292-5p 抑制剂组相比,miR-292-5p 抑制剂组室性心动过速和室颤的发生率和持续时间降低,血清心肌酶、TNF-α、IL-6、IL-1β、MDA、心肌细胞凋亡、Bax 和 p53 表达增加,SOD 和 GSH-Px 活性增加,Bcl-2、PPARα、PPARγ、PLIN5、AQP7 和 PCK1 表达增加。T0070907 组与 miR-292-5p 抑制剂组的结果相反。结果表明,miR-292-5p 的下调通过激活 PPAR-α/PPAR-γ 信号通路来保护心肌免受 IRI。

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