Y-27632, a Rho-kinase inhibitor, attenuates myocardial ischemia-reperfusion injury in rats
Y-27632, a Rho-kinase inhibitor, attenuates myocardial ischemia-reperfusion injury in rats
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DOI：
10.3892/ijmm.2019.4097
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发表时间：
2019-04-01
影响因子：
5.4
通讯作者：
Xue, Song
中科院分区：
文献类型：
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作者：
Dong, Li-Ya;Qiu, Xiao-Xiao;Xue, Song
本研究旨在评价Rho激酶抑制剂Y-27632的心脏保护作用及其机制。结扎大鼠冠状动脉建立心肌缺血再灌注（I/R）损伤模型，采用Langendorff系统进行离体大鼠心脏全脑缺血。用氯化三苯基四氮唑（TTC）和苏木精-伊红染色，分析心肌梗死面积和组织病理学改变的I/R诱导的大鼠心脏。此外，还分析了冠状动脉血流、心肌收缩力和心电图。通过ELISA评估Y-27632对血清中炎性细胞因子和心肌酶的影响。凋亡和炎症相关蛋白的表达也通过蛋白质印迹分析。TTC染色和组织病理学诊断显示Y-27632组大鼠心肌I/R损伤减轻。此外，Y-27632恢复了ST段。离体大鼠心脏冠脉流量和心肌收缩力的数据表明，Y-27632改善I/R后的心功能。Y-27632下调血清中炎性细胞因子和心肌酶的水平。丝裂原活化蛋白激酶（MAPK）和核因子（NF）-κ B信号通路被Y-27632抑制。此外，Y-27632有效地抑制大鼠和离体心脏中的凋亡相关蛋白的表达。总之，本研究的结果表明，Y-27632通过抑制MAPK和NF-κ B信号通路的激活来减轻心肌损伤;因此，细胞凋亡和炎症反应被抑制。
The present study aimed to evaluate the cardio-protective effects of a Rho-kinase inhibitor, Y-27632, and the underlying mechanisms. A rat model of myocardial ischemia-reperfusion (I/R) injury was generated by ligation of the coronary artery, and global ischemia of isolated rat hearts was conducted using the Langendorff system. Staining with triphenyltetrazolium chloride (TTC) and hematoxylin and eosin was performed to analyze the myocardial infarct size and histopathological alterations of the I/R-induced rat heart. In addition, coronary flow, myocardial contractility and an electrocardiogram were analyzed. The effects of Y-27632 on inflammatory cytokines and cardiac enzymes in the serum were assessed by ELISA. The expression of apoptosis- and inflammation-associated proteins was also analyzed via western blotting. Rats in the Y-27632 group exhibited alleviated myocardial I/R injury according to TTC staining and histopathological diagnosis. Additionally, Y-27632 restored the ST segment. The data of coronary flow and myocardial contractility in isolated rat hearts indicated that Y-27632 improved heart function following I/R. The levels of inflammatory cytokines and cardiac enzymes in the serum were downregulated by Y-27632. The mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-kappa B signaling pathways were inhibited by Y-27632. Furthermore, apoptosis-associated protein expression in rats and the isolated hearts was effectively inhibited by Y-27632. In conclusion, the findings of the present study indicated that Y-27632 attenuated myocardial injury via inhibiting the activation of the MAPK and NF-kappa B signaling pathways; thus, apoptosis and the inflammatory response were suppressed.