α_(2)-肾上腺素能受体激动剂对心肌炎大鼠ERK1/2和AKT信号通路的影响研究  

Study of effects of α_(2)-adrenergic receptor agonists on ERK1/2 and AKT signaling pathways in rats with myocarditis

作　　者：丁同斌[1] 刘航 栗媛 简立国[1] DING Tongbin;LIU Hang;LI Yuan;JIAN Liguo(Cardiology Department,the Second Affiliated Hospital of Zhengzhou University,Zhengzhou 450014,China)

机构地区：[1]郑州大学第二附属医院心内科,河南郑州450014

出　　处：《临床医学研究与实践》2021年第22期1-4,10,共5页Clinical Research and Practice

基　　金：河南省医学科技攻关计划项目(No.SBGJ202002088)。

摘　　要：目的研究α_(2)-肾上腺素能受体(α_(2)-AR)激动剂对心肌炎大鼠ERK1/2和PI3K/AKT信号通路的影响。方法采用完全弗氏佐剂及猪心肌肌球蛋白感染易致敏的Lewis大鼠,构建实验性自身免疫性心肌炎(EAM)大鼠模型,将大鼠随机分为对照组、EAM模型组(EAM组)、α_(2)-AR激动剂组(EAM+α_(2)-AR组)、PI3K/AKT信号通路抑制剂组(EAM+α_(2)-AR+EAM-LY组)和ERK1/2信号通路抑制剂组(EAM+α_(2)-AR+U0126组),每组6只。超声心动图检查心率、EF、FS、LVEDD和LVEDS,HE染色检测大鼠心肌组织病理学情况,蛋白质免疫印迹法检测p-AKT、p-ERK1/2、Caspase-3、PARP蛋白的相对表达量,TUNEL染色检测大鼠心肌细胞凋亡情况。结果与对照组比较,EAM组大鼠的心率、LVEDD和LVEDS升高,EF和FS降低(P<0.01)。与EAM组比较,EAM+α_(2)-AR组大鼠心肌组织病变程度减轻;EAM+α_(2)-AR组大鼠炎性评分降低(P<0.01)。与EAM组比较,EAM+α_(2)-AR组大鼠心肌组织中p-AKT蛋白的相对表达量上调,p-ERK1/2、Caspase-3和PARP蛋白的相对表达量下调,ROS水平下降(P<0.01)。与EAM+α_(2)-AR组比较,EAM+α_(2)-AR+EAM-LY组大鼠心肌组织中p-AKT蛋白的相对表达量下调,细胞凋亡率升高(P<0.01);EAM+α_(2)-AR+U0126组大鼠心肌组织中p-ERK1/2蛋白相对表达量下调,细胞凋亡率降低(P<0.01)。结论α_(2)-AR激动剂可能通过激活PI3K/AKT信号通路和抑制ERK1/2信号通路的方式,下调Caspase-3和PARP蛋白的相对表达水平,降低ROS水平,从而缓解心肌炎大鼠的炎症反应、抑制其细胞凋亡,起到保护心肌的作用。Objective To study the effects ofα_(2)-adrenergic receptor(α_(2)-AR)agonist on ERK1/2 and PI3K/AKT signaling pathways in rats with myocarditis.Methods Sensitized Lewis rats were infected with complete Freund's adjuvant and porcine myocardial myosin to establish experimental autoimmune myocarditis(EAM)rats model,and the rats were randomly divided into control group,EAM model group(EAM group),α_(2)-AR agonist group(EAM+α_(2)-AR group),PI3K/AKT signal pathway inhibitor group(EAM+α_(2)-AR+EAM-LY group)and ERK1/2 signal pathway inhibitor group(EAM+α_(2)-AR+U0126 group),with 6 rats in each group.The heart rate,EF,FS,LVEDD and LVEDS were detected by echocardiography,myocardial histopathology of rats were detected by HE staining,the relative expression of p-AKT,p-ERK1/2,Caspase-3 and PARP protein were detected by Western blot,and the apoptosis of cardiomyocytes of rats was detected by TUNEL staining.Results Compared with the control group,the heart rate,LVEDD and LVEDS of the EAM group increased,while EF and FS decreased(P<0.01).Compared with the EAM group,the degree of pathological in the EAM+α_(2)-AR group changes alleviated;the inflammatory score of myocardium tissue in the EAM+α_(2)-AR group decreased(P<0.01).Compared with the EAM group,the relative expression of p-AKT protein in the myocardium of rats in the EAM+α_(2)-AR group up-regulated,the relative expression of p-ERK1/2,Caspase-3 and PARP protein down-regulated,and the ROS level decreased(P<0.01).Compared with the EAM+α_(2)-AR group,the relative expression of p-AKT protein in the myocardium of rats in the EAM+α_(2)-AR+EAM-LY group down-regulated,and the apoptosis rate increased(P<0.01);the relative expression of p-ERK1/2 protein in the myocardium of rats in the EAM+α_(2)-AR+U0126 group down-regulated,and the apoptosis rate decreased(P<0.01).Conclusion By activating PI3K/AKT signaling pathway and inhibiting ERK1/2 signaling pathway,α_(2)-AR agonist may down regulate the relative expression levels of Caspase-3 and PARP protein,reduce ROS level,so as

关 键 词：α_(2)-肾上腺素能受体激动剂 心肌炎 ERK1/2 AKT 氧化应激 

分 类 号：R542.2[医药卫生—心血管疾病]