Liu Yan, Zou Jianfeng, Liu Xiaoyan, Zhang Quan
The First Ward, Department of Cardiology, Rizhao People's Hospital, Rizhao, Shandong 276800, P.R. China.
The Third Ward, Department of Cardiology, Rizhao People's Hospital, Rizhao, Shandong 276800, P.R. China.
Exp Ther Med. 2019 Nov;18(5):3325-3332. doi: 10.3892/etm.2019.7976. Epub 2019 Sep 5.
Myocardial ischemia-reperfusion (I/R) injury is considered to have a detrimental role in coronary heart disease, which is considered to be the leading cause of death worldwide. However, the molecular mechanism involved in the progression of myocardial I/R injury is still unclear. The current study aimed to investigate the expression and function of microRNA (miR)-138 in the process of myocardial I/R injury. First, miR-138 expression levels were analyzed both in myocardium with I/R injury and control myocardium using reverse transcription-quantitative polymerase chain reaction analysis. Then, the relationship between the levels of miR-138 and hypoxia-inducible factor (HIF)1-α was also investigated using a luciferase reporter assay. Assessment of myocardial infarct size, measurements of serum myocardial enzymes and electron microscopy analysis were all utilized to analyse the effect of miR-138 on myocardial I/R injury. The authors of current study also used western blotting to examine the expression levels of the mitochondrial fission-related proteins dynamin-1-like protein and mitochondrial fission 1 protein. It was found that miR-138 is downregulated and HIF1-α is upregulated after myocardial ischemia reperfusion injury. Overexpression of miR-138 reduced myocardial I/R injury-induced infarct sizes and myocardial enzyme levels, and it also inhibited the expression of proteins related to mitochondrial morphology and myocardial I/R-induced mitochondrial apoptosis by targeting HIF1-α. Taken together, these findings provide a novel insight into the molecular mechanism of miR-138 and HIF1-α in the progression of myocardial I/R injury. miR-138 has the potential to become a promising therapeutic target for treating myocardial I/R injury.
心肌缺血再灌注（I/R）损伤被认为在冠心病中起有害作用，而冠心病被认为是全球主要的死亡原因。然而，心肌I/R损伤进展过程中涉及的分子机制仍不清楚。当前研究旨在探讨微小RNA（miR）-138在心肌I/R损伤过程中的表达及功能。首先，采用逆转录-定量聚合酶链反应分析，对I/R损伤心肌和对照心肌中的miR-138表达水平进行分析。然后，还使用荧光素酶报告基因检测法研究了miR-138水平与缺氧诱导因子（HIF）1-α之间的关系。利用评估心肌梗死面积、检测血清心肌酶以及电子显微镜分析，来分析miR-138对心肌I/R损伤的影响。本研究的作者还使用蛋白质印迹法检测了线粒体分裂相关蛋白动力蛋白样蛋白1和线粒体分裂蛋白1的表达水平。研究发现，心肌缺血再灌注损伤后miR-138表达下调，HIF1-α表达上调。miR-138过表达可减小心肌I/R损伤诱导的梗死面积和心肌酶水平，还可通过靶向HIF1-α抑制与线粒体形态及心肌I/R诱导的线粒体凋亡相关的蛋白表达。综上所述，这些发现为miR-138和HIF1-α在心肌I/R损伤进展中的分子机制提供了新的见解。miR-138有潜力成为治疗心肌I/R损伤的一个有前景的治疗靶点。
