Department of Internal Medicine, Hebei Medical University, Shijiazhuang City, Hebei Province 050011, China.
Department of Cardiology, First Hospital of Qinhuangdao, Qinhuangdao City, Hebei Province 066000, China.
Biochem Cell Biol. 2020 Jun;98(3):378-385. doi: 10.1139/bcb-2019-0310. Epub 2020 May 15.
Myocardial ischemia-reperfusion injury (MIRI) is the leading cause of the poor prognosis for patients undergoing clinical cardiac surgery. Micro-RNAs are involved in MIRI; however, the effect of miR-760 on MIRI and the molecular mechanisms behind it have not yet been described. For our in-vivo experiments, 20 rats were randomly distributed between 2 groups ( = 10): the sham-treatment group and the ischemia-reperfusion (I/R) group. For our in-vitro experiments, H9C2 cells were subjected to hypoxia for 6 h, and then reoxygenated to establish an hypoxia-reoxygenation (H/R) model. High expression levels of of miR-760 were observed in the rats subjected to MIRI and the H9C2 cells subjected to H/R. Further, the levels of lactate dehydrogenase (LDH) and malonaldehyde (MDA) were increased, and the size of the myocardial infarct was notably greater in the rats subjected to MIRI, suggesting that miR-760 worsens the effects of MIRI. The inhibitory effects from NaHS on apoptosis were enhanced, as were the expression levels of cleaved caspase 3 and cleaved PARP in H9C2 cells exposed to H/R, and with low-expression levels of miR-760. TargetScan and dual luciferase reporter assays further confirmed the targeted relationship between dual-specificity protein phosphatase (DUSP1) and miR-760. Additionally, miR-760 overexpression and H/R treatment of H9C2 cells inhibited the expression of DUSP1, which further promoted apoptosis. Furthermore, DUSP1 enhanced the anti-apoptotic effects of NaHS in rats subjected to MIRI. Taken together, these findings suggest that miR-760 inhibits the protective effect of NaHS against MIRI.
心肌缺血再灌注损伤（MIRI）是导致接受临床心脏手术的患者预后不良的主要原因。微小 RNA（miRNA）参与 MIRI；然而，miR-760 对 MIRI 的影响及其背后的分子机制尚未描述。对于我们的体内实验，20 只大鼠随机分为 2 组（n=10）：假手术组和缺血再灌注（I/R）组。对于我们的体外实验，H9C2 细胞在缺氧 6 小时后再氧合，建立缺氧再氧合（H/R）模型。在经历 MIRI 的大鼠和经历 H/R 的 H9C2 细胞中观察到 miR-760 的高表达水平。此外，在经历 MIRI 的大鼠中，乳酸脱氢酶（LDH）和丙二醛（MDA）的水平升高，心肌梗死面积明显增大，表明 miR-760 加重了 MIRI 的影响。在 H9C2 细胞中，NaHS 对凋亡的抑制作用增强，并且在经历 H/R 的 H9C2 细胞中，cleaved caspase 3 和 cleaved PARP 的表达水平也升高，miR-760 的表达水平较低。TargetScan 和双荧光素酶报告基因实验进一步证实了双特异性蛋白磷酸酶（DUSP1）和 miR-760 之间的靶向关系。此外，miR-760 过表达和 H/R 处理 H9C2 细胞抑制了 DUSP1 的表达，进一步促进了细胞凋亡。此外，DUSP1 增强了 NaHS 在经历 MIRI 的大鼠中的抗凋亡作用。总之，这些发现表明 miR-760 抑制了 NaHS 对 MIRI 的保护作用。
