β2AR激动剂通过线粒体细胞凋亡途径改善大鼠心肌缺血再灌注损伤  

β2-adrenergic receptor agonist improves myocardial ischemia-reperfusion injury in rats through mitochondrial apoptosis pathway

作　　者：刘通 史静怡 王利[1] 闫泱锦 程康 冀永春 LIU Tong;SHI Jingyi;WANG Li;YAN Yangjin;CHENG Kang;JI Yongchun(Department of Cardiovascular Medicine,Xi’an Third Hospital,Affiliated Hospital of Northwest University,Xi’an 710018,China)

机构地区：[1]西安市第三医院,西北大学附属医院心血管内科,西安710018

出　　处：《山西医科大学学报》2020年第12期1335-1340,共6页Journal of Shanxi Medical University

基　　金：西安市科技计划项目(201805094YX2SF(7))。

摘　　要：目的研究β2肾上腺素能受体激动剂(clenbuterol)对大鼠心肌缺血再灌注损伤的影响以及与线粒体细胞凋亡途径的关系。方法将40只SD大鼠分为假手术组、模型组和实验组。构建大鼠心肌缺血再灌注损伤模型,实验组大鼠在模型组的基础上给予clenbuterol(0.5 mg/kg)处理。采用心电图观察大鼠心肌缺血再灌注心律失常现象,采用HE染色以及透射电镜观察组织病理状态以及线粒体形态,采用实时聚合酶链反应(RT-PCR)检测β2AR、Caspase-3、Bax、Cx43和PKC-εmRNA表达水平,采用蛋白质免疫印迹法检测以上基因的蛋白表达水平,采用全自动生化分析仪测定各组血清中CK-MB及LDH的含量。结果HE染色以及透射电镜结果显示,实验组大鼠心肌细胞坏死和线粒体肿胀较模型组得到明显的改善。与模型组相比,实验组大鼠心肌组织中β2AR的mRNA和蛋白表达量均显著上调(P<0.05)。与假手术组比较,模型组及实验组大鼠血清中CK-MB及LDH含量均显著升高(P<0.05),且实验组大鼠血清中CK-MB及LDH含量均显著低于模型组(P<0.05)。与假手术组比较,模型组大鼠心肌组织中Bax和Caspase-3蛋白表达水平显著上调,Cx43和PKC-ε蛋白表达水平显著下调(P<0.05)。与模型组比较,实验组大鼠心肌组织中Bax和Caspase-3蛋白表达水平较模型组显著下调,Cx43和PKC-ε蛋白表达水平显著上调(P<0.05)。结论β2肾上腺素能受体激动剂(clenbuterol)能明显改善心肌缺血再灌注损伤,而这种作用主要是通过调节线粒体细胞凋亡途径实现。Objective To study the effect ofβ2-adrenergic receptor agonist(clenbuterol)on myocardial ischemia-reperfusion injury and its relationship with mitochondrial cell apoptosis pathway.Methods Forty SD rats were divided into sham operation group,model group and experimental group.A rat model of myocardial ischemia-reperfusion injury was constructed,and the rats in experimental group were treated with clenbuterol(0.5 mg/kg)based on the treatment in model group.Electrocardiogram was used to observe the myocardial ischemia-reperfusion arrhythmia.HE staining and transmission electron microscopy were used to observe the pathological state and mitochondrial morphology.Real-time polymerase chain reaction(RT-PCR)was used to detect the mRNA expression levels ofβ2AR,Caspase-3,Bax,Cx43,PKC-ε.Western blotting was used to detect the protein levels of the above genes.And automatic biochemical analyzer was used to determine the contents of CK-MB and LDH in the serum of each group.Results HE staining and transmission electron microscopy showed that myocardial cell necrosis and mitochondrial swelling in experimental group were significantly improved.Compared with model group,the mRNA and protein expression levels ofβ2AR in the myocardial tissue were significantly increased in experimental group(P<0.05).Compared with sham group,the serum CK-MB and LDH levels were significantly increased in model group and experimental group(P<0.05),and the serum CK-MB and LDH levels in experimental group were significantly lower than those in model group(P<0.05).Compared with sham group,the expression levels of Bax and Caspase-3 protein in the myocardial tissue were significantly up-regulated in model group,and the Cx43 and PKC-εprotein expression levels were significantly down-regulated(P<0.05).Compared with model group,the expression levels of Bax and Caspase-3 protein in myocardial tissue in experimental group were significantly down-regulated,and the expression levels of Cx43 and PKC-εprotein were significantly up-re-gulated(P<0.05).Conclusio

关 键 词：β2肾上腺素能受体激动剂(clenbuterol) 心肌缺血再灌注损伤 线粒体 细胞凋亡 

分 类 号：R363[医药卫生—病理学]