Ras同源基因家族蛋白A/Rho相关卷曲螺旋蛋白激酶抑制剂对冠状动脉微栓塞引起心肌损伤的预防作用  

RhoA/ROCK Signaling Pathway Inhibitor Y-27632 Reduces Myocardial Apoptosis and Micro-infarct Area in Rats With Coronary Microembolism

作　　者：吴永辉[1] 聂绍平[2] 任凤学[1] 刘超永 WU Yonghui;NIE Shaoping;REN Fengxue;LIU Chaoyong(Department of Cardiology,General Aviation Hospital,China Medical University,Beijing,100012,China)

机构地区：[1]中国医科大学航空总医院心内科,北京市100012 [2]首都医科大学附属北京安贞医院急诊科

出　　处：《中国循环杂志》2021年第7期705-711,共7页Chinese Circulation Journal

摘　　要：目的:探讨Ras同源基因家族蛋白A(Rho A)/Rho相关卷曲螺旋蛋白激酶(ROCK)信号通路在冠状动脉微栓塞(CME)大鼠心肌凋亡的作用机制。方法:将60只SD大鼠随机分为3组:假手术组、模型组、抑制剂组;模型组、抑制剂组经左心室注入微栓塞球构建CME模型;构建CME模型前1 h抑制剂组尾静脉注射RhoA/Rho信号通路抑制剂(Y-27632)(5 mg/kg)。术后12 h依次采用:苏木素碱性品红苦味酸(HBFP)染色、脱氧核糖核苷酸末端转移酶介导的缺口末端标记(TUNEL)染色、免疫印迹法(Western blot)检测心肌缺血微梗死面积、心肌细胞的凋亡率以及p-RhoA、ROCK1、ROCK2的表达水平。结果:与假手术组相比,模型组大鼠心脏的微梗死面积、心肌细胞凋亡率、p-RhoA、ROCK1、ROCK2的表达明显升高,与模型组相比,抑制剂组大鼠的心脏的微梗死面积、心肌细胞凋亡率、p-RhoA、ROCK1、ROCK2的表达明显降低,差异均有统计学意义(均P<0.05)。结论:CME激活RhoA/ROCK通路,抑制RhoA/ROCK通路能明显降低心肌的凋亡率,改善CME大鼠心功能。Objectives:To explore the role of the Ras homolog gene family member A(Rho A)/Rho-associated coiled-coil forming protein kinase(ROCK)signaling pathway in myocardial apoptosis in rats with coronary microembolism.Methods:Sixty SD rats were randomly divided into three groups:sham group,model group and inhibitor group.Rats in model group and inhibitor group were injected with microembolism ball into the left ventricle to establish CME model.The rats in the inhibitor group were injected with Y-27632(5 mg/kg)into the tail vein 1 h before the establishment of CME model.After 12h,haematoxylin basic fuschin picric acid stain(HBFP)staining,TdT-mediated dUTP nick labeling(TUNEL)staining,Western blot were used to detect myocardial ischemic micro-infarct area,myocardial cell apoptosis rate,and myocardial expression levels of p-RhoA,ROCK1,and ROCK2.Results:The micro-infarct area,cardiomyocyte apoptosis rate,p-RhoA,the expression of myocardial ROCK1 and ROCK2 were significantly increased in the model group than in the sham group(all P<0.05).Compared with the model group,the micro-infarct area,cardiomyocyte apoptosis rate,p-RhoA,the myocardial expression of ROCK1 and ROCK2 in the model group were significantly decreased(all P<0.05).Conclusions:RhoA/ROCK pathway is activated in CME rats,and inhibition of RhoA/ROCK pathway can significantly reduce myocardial apoptosis rate and improve cardiac function in CME rats.

关 键 词：冠状动脉微栓塞 RhoA/ROCK通路 心肌凋亡 

分 类 号：R54[医药卫生—心血管疾病]