普萘洛尔对糖尿病模型大鼠心肌异常电生理效果的影响及机制  

Effect and Mechanism of Propranolol on the Myocardial Abnormal Electrophysiology Station in Diabetic Model Rats

作　　者：刘军[1] 王昕[1] 邓骥[1] 贾静[1] 肖静[1] 

机构地区：[1]湖北医药学院附属襄阳医院药学部,湖北襄阳441000

出　　处：《中国药房》2016年第10期1357-1359,共3页China Pharmacy

摘　　要：目的:研究普萘洛尔对糖尿病模型大鼠心肌异常电生理效果的影响及机制。方法:取SD大鼠随机分为正常对照(生理盐水)组、糖尿病(生理盐水)组、PD98059[细胞外信号转导(ERK)抑制剂,10 mg/kg]组和普萘洛尔低、中、高剂量(1、20、50 mg/kg)组,每组8只。除正常对照组外其余各组大鼠一次性尾iv四氧嘧啶(20 mg/kg)复制糖尿病模型,各组大鼠ig相应药物,每日1次,连续给药42 d。分析各组大鼠心脏指数、体表心电图、右心室乳头肌跨膜电位(APD)变化;检测血清中肿瘤坏死因子α(TNF-α)、白细胞介素(IL)-2、IL-6、IL-10蛋白表达和心肌组织中大鼠肉瘤蛋白(Ras)、快速反应肉瘤蛋白(Raf)、ERK激酶(MEK)及细胞外调节激酶1/2(ERK1/2)的表达。结果:与正常对照组比较,糖尿病组大鼠心脏指数增加,心率降低,QT间期和APD延长,TNF-α、IL-2、IL-6、IL-10、Ras、Raf、MEK及ERK1/2蛋白的相对表达量均增强(P<0.01)。与糖尿病组比较,普萘洛尔中、高剂量组和PD98059组大鼠心脏指数降低,心率增加,QT间期和APD缩短,TNF-α、IL-2、IL-6、IL-10、Ras、Raf、MEK及ERK1/2蛋白的相对表达量均降低(P<0.05或P<0.01)。结论:普萘洛尔可改善糖尿病模型大鼠心肌异常电生理效果,其可能是通过下调血清中炎症反应和抑制MEK/ERK通路的激活而发挥作用。OBJECTIVE：To study the effects and mechanism of propranolol on the myocardial abnormal electrophysiology station in diabetic model rats. METHODS：SD rats were randomly divided into normal control（normal saline）group,diabetic（normal saline）group,PD98059（ERK inhibitor,10 mg/kg）group and propranolol low-dose,medium-dose and high-dose（1,20,50mg/kg）groups,with 8 rats in each group. Except for normal control group,rats were given alloxan（20 mg/kg）intravenously via tail vein to induce diabetic model. They were given relevant medicine intragastrically,once a day,for consecutive 42 days. The cardiac index,electrocardiogram and action potential durations（APD） of rats were analyzed;the expression of TNF-α,IL-2,IL-6and IL-10 protein in serum were detected,and the expression of Ras,Raf,ERK kinase（MEK）and ERK1/2 in myocardial tissue were detected. RESULTS：Compared with normal control group,cardiac index increased in diabetes group;heart rate decreased;QT interval and APD were prolonged;the relative expression of TNF-α,IL-2,IL-6,IL-10,Ras,Raf,MEK and ERK1/2 protein increased（P0.01）. Compared with diabetes group,cardiac index decreased in propranolol medium-dose and high-dose groups and PD98059 group,heart rate increased,QT interval and APD were shortened;the relative expression of TNF-α,IL-2,IL-6,IL-10,Ras,Raf,MEK and ERK1/2 protein decreased（P0.05 or P0.01）. CONCLUSIONS：Propranolol can improve myocardial abnormal electrophysiology station of diabetic model rats by down-regulating inflammatory reactions in serum and inhibiting the activation of MEK/ERK signaling pathway.

关 键 词：糖尿病 普萘洛尔 心肌异常 电生理 细胞外信号转导激酶/细胞外信号转导信号通路 炎症反应 大鼠 

分 类 号：R965[医药卫生—药理学]