Sun Tao, Gong Qian, Wu Ying, Shen Zhiming, Zhang Yan, Ge Shenglin, Duan Jing-Si
Department of Cardiovascular Surgery, The First Affiliated Hospital of Anhui Medical University, No. 218, Jixi Road, Shushan District, Hefei, 230032, Anhui, China.
Yangzhou University Medical College, Yangzhou, 225001, Jiangsu, China.
Naunyn Schmiedebergs Arch Pharmacol. 2021 Jul;394(7):1569-1577. doi: 10.1007/s00210-021-02082-6. Epub 2021 Mar 29.
The global incidence of myocardial infarction has been consistently high, and it is one of the main causes of poor cardiovascular prognosis. Dexmedetomidine (DEX) is a highly selective α2 receptor agonist. Recent studies have found that DEX has a protective effect on myocardial infarction, but its specific mechanism is still unclear. In this experiment, we permanently ligated the anterior descending branch of mice to explore the protective mechanism of DEX against myocardial infarction. Our study found that intraperitoneal injection of DEX for 7 days after myocardial infarction in mice can increase the reduction of ejection fraction (EF) and fractional shortening (FS) caused by myocardial infarction and significantly reduce the release of serum markers. The results of myocardial HE and Sirius red staining suggest that the changes in the myocardial structure of mice after using DEX are reduced. Immunohistochemistry shows that DEX reduces the expression of ROCK1 protein after myocardial infarction. TUNEL staining and the protein expression levels of cleaved caspase-3 and cleaved caspase-9 were used to detect cell apoptosis and results make clear that DEX can reduce the apoptosis caused by myocardial infarction. Western blot experiments showed that DEX can reduce the expression levels of ROCK1 and ROCK2 (Rho-kinase). At the same time, it was observed that DEX improved the Bcl-2/Bax ratio. The above results indicate that DEX reduces cardiomyocyte apoptosis and improves cardiac function likely through inhibiting the RhoA/ROCK signaling pathway. This study may provide new insights into the protective effect of DEX after myocardial infarction in mice.
心肌梗死的全球发病率一直居高不下，是心血管预后不良的主要原因之一。右美托咪定（DEX）是一种高度选择性的α2受体激动剂。最近的研究发现，DEX对心肌梗死具有保护作用，但其具体机制仍不清楚。在本实验中，我们永久性结扎小鼠的前降支，以探讨DEX对心肌梗死的保护机制。我们的研究发现，小鼠心肌梗死后腹腔注射DEX 7天，可以增加心肌梗死引起的射血分数（EF）降低和缩短分数（FS），并显著降低血清标志物的释放。心肌HE和天狼星红染色结果表明，使用DEX后小鼠心肌结构的变化减少。免疫组织化学显示，DEX可降低心肌梗死后ROCK1蛋白的表达。采用TUNEL染色及裂解的caspase-3和裂解的caspase-9蛋白表达水平检测细胞凋亡，结果表明DEX可减少心肌梗死引起的细胞凋亡。蛋白质印迹实验表明，DEX可降低ROCK1和ROCK2（Rho激酶）的表达水平。同时，观察到DEX改善了Bcl-2/Bax比值。上述结果表明，DEX可能通过抑制RhoA/ROCK信号通路减少心肌细胞凋亡并改善心脏功能。本研究可能为DEX对小鼠心肌梗死后的保护作用提供新的见解。
