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
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篇名: | 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 |
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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。 |
ABSTRACT: | 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, 50 mg/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-6 and 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 (P<0.01). 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 (P<0.05 or P<0.01). 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. |
期刊: | 2016年第27卷第10期 |
作者: | 刘军,王昕,邓骥,贾静,肖静 |
AUTHORS: | LIU Jun,WANG Xin,DENG Ji,JIA Jing,XIAO Jing |
关键字: | 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 |
KEYWORDS: | Diabetes; Propranolol; Myocardial abnormality; Electrophysiology station; MEK/ERK signaling pathway; Inflammatory reaction; Rats |
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