Bian Bo, Yu Xue-Fang, Wang Guo-Qin, Teng Tian-Ming
Cardiology Department, Tianjin Medical University General Hospital, Tianjin, China.
Cardiology Department, Tianjin Medical University General Hospital, Tianjin, China.
Cardiovasc Pathol. 2017 Mar-Apr;27:37-42. doi: 10.1016/j.carpath.2016.12.006. Epub 2017 Jan 3.
MiRNA-1 may participate in regulating ischemia-reperfusion injury (IRI) by affecting the expression and distribution of connexin 43 (Cx43). The aim of this study is to investigate miR-1 expression and its potential role in regulating Cx43 during ischemic postconditioning (IPOST) in a rat model. Fifty-five Wistar male rats were randomly divided into five groups: N, IR, IPOST, agomir-1, and antagomir-1 group. The hearts were perfused with the Langendorff system. The reperfusion arrhythmia (RA) and myocardial infarct size were observed and recorded. The miRNA-1 expression and the Cx43 expression and distribution were assessed by RT-PCR, immunoblotting, and immunohistochemistry. First, the RA score in the IR group was higher than that in the control group, whereas there was no difference between the IPOST and antagomir-1 groups. Second, the myocardial infarct size was larger in the agomir-1 than in the IPOST group; there was no difference between the antagomir-1 and the IPOST group. Third, the miRNA-1 expression increased by 78% in the agomir-1 group but decreased by 32% in the antagomir-1 group compared with the IPOST group. Fourth, compared with the Control group, the Cx43 expression in the IR group decreased, the Cx43 expression decreased in the agomir-1 group compared with the IPOST group. Fifth, the distribution of Cx43 was irregular and disorganized in the IR and agomir-1 groups. In the IPOST and antagomir-1 groups, Cx43 was neatly distributed in the intercalated disk area. Our findings suggest that IPOST can inhibit the up-regulation of miRNA-1 induced by ischemia-reperfusion and that the down-regulation of miRNA-1 can prevent the decrease and redistribution of Cx43, which will protect the heart from IRI.
微小RNA-1（MiRNA-1）可能通过影响连接蛋白43（Cx43）的表达和分布参与调节缺血再灌注损伤（IRI）。本研究旨在探讨大鼠模型中缺血后处理（IPOST）期间miR-1的表达及其在调节Cx43中的潜在作用。55只Wistar雄性大鼠随机分为五组：N组、IR组、IPOST组、agomir-1组和antagomir-1组。采用Langendorff系统对心脏进行灌注。观察并记录再灌注心律失常（RA）和心肌梗死面积。通过逆转录聚合酶链反应（RT-PCR）、免疫印迹和免疫组织化学评估miRNA-1表达以及Cx43表达和分布。首先，IR组的RA评分高于对照组，而IPOST组和antagomir-1组之间无差异。其次，agomir-1组的心肌梗死面积大于IPOST组；antagomir-1组和IPOST组之间无差异。第三，与IPOST组相比，agomir-1组的miRNA-1表达增加了78%，而antagomir-1组降低了32%。第四，与对照组相比，IR组的Cx43表达降低，agomir-1组与IPOST组相比Cx43表达降低。第五，IR组和agomir-1组中Cx43的分布不规则且紊乱。在IPOST组和antagomir-1组中，Cx43整齐地分布在闰盘区域。我们的研究结果表明，IPOST可抑制缺血再灌注诱导的miRNA-1上调，miRNA-1的下调可防止Cx43的减少和重新分布，从而保护心脏免受IRI损伤。
