Wang Xian-Tao, Wu Xiao-Dan, Lu Yuan-Xi, Sun Yu-Han, Zhu Han-Hua, Liang Jia-Bao, He Wen-Kai, Zeng Zhi-Yu, Li Lang
Cell Physiol Biochem. 2017;44(5):1995-2004. doi: 10.1159/000485905. Epub 2017 Dec 11.
BACKGROUND/AIMS: Coronary microembolization (CME) can lead to no-reflow or slow reflow, which is one of the important reasons for loss of clinical benefit from myocardial reperfusion therapy. MicroRNAs and autophagy are heavily implicated in the occurrence and development of almost all cardiovascular diseases. Therefore, the present study was designed to investigate the role of miR-30e-3p and autophagy in CME-induced myocardial injury rat model.
Sixty rats were randomly divided into six groups: sham, CME 1h,3h,6h,9h, and 12h (n = 10 per group). Our CME rat model was created by injecting polyethylene microspheres (42mm) into the left ventricle of the heart; the sham group was injected with same volume of normal saline. The cardiac function and serum cardiac troponin I (cTnI) level of each group was measured. HE staining and HBFP staining were used to evaluate the myocardial micro-infarction area of myocardium tissue samples. Then RT-qPCR and western blot were used to detect the expression of miR-30e-3p and, autophagy related protein LC3-II and p62, respectively. Transmission electron microscope (TEM) was used to identify autophagic vacuoles in tissue samples.
The cardiac function of the CME 6h,9h, and 12h groups were significantly decreased compared to the sham group (P < 0.05) and the cTnI level in each group were also significantly increased (P < 0.05). The expression of miR-30e-3p in the CME 6h, 9h and 12h group were decreased significantly compared with the sham group (P < 0.05). Meanwhile, the expression of autophagy related protein LC3-II decreased significantly and p62 increased significantly in the CME 9h and 12h group (P < 0.05). TEM images showed typical autophagic vacuoles for each of the CME groups.
Myocardial miR-30e-3p is down regulated after CME and is accompanied by inhibited autophagy and decreased cardiac function. Therefore, miR-30e-3p may be involved in CME-induced cardiac dysfunction by regulating myocardial autophagy.
背景/目的：冠状动脉微栓塞（CME）可导致无复流或慢复流，这是心肌再灌注治疗临床获益丧失的重要原因之一。微小RNA和自噬在几乎所有心血管疾病的发生和发展中都起着重要作用。因此，本研究旨在探讨miR-30e-3p和自噬在CME诱导的心肌损伤大鼠模型中的作用。
将60只大鼠随机分为六组：假手术组、CME 1小时组、3小时组、6小时组、9小时组和12小时组（每组n = 10）。通过将聚乙烯微球（42μm）注入心脏左心室建立CME大鼠模型；假手术组注射等量生理盐水。测量每组的心脏功能和血清心肌肌钙蛋白I（cTnI）水平。采用HE染色和HBFP染色评估心肌组织样本的心肌微梗死面积。然后分别用RT-qPCR和western blot检测miR-30e-3p以及自噬相关蛋白LC3-II和p62的表达。用透射电子显微镜（TEM）鉴定组织样本中的自噬泡。
与假手术组相比，CME 6小时组、9小时组和12小时组的心脏功能显著降低（P < 0.05），且每组的cTnI水平也显著升高（P < 0.05）。与假手术组相比，CME 6小时组、9小时组和12小时组中miR-30e-3p的表达显著降低（P < 0.05）。同时，CME 9小时组和12小时组中自噬相关蛋白LC3-II的表达显著降低，p62的表达显著升高（P < 0.05）。TEM图像显示每个CME组都有典型的自噬泡。
CME后心肌miR-30e-3p下调，并伴有自噬受抑制和心脏功能降低。因此，miR-30e-3p可能通过调节心肌自噬参与CME诱导的心脏功能障碍。
