钩藤碱对自发性高血压大鼠心室重构过程中TGF-β_1/Smad通路的影响  

Effect of rhynchophylline on TGF-β_1/ Smad pathway for processing ventricular remodeling in spontaneously hypertensive rats

作　　者：黄华[1] 李宇声 金鑫[1] 汪江涛 李娜[1] 黄帧桧[1] 丁伯平[1] 

机构地区：[1]皖南医学院药理学教研室及国家中医药管理局中药药理三级实验室 [2]皖南医学院 [3]芜湖市中医医院,安徽芜湖241002

出　　处：《中国病理生理杂志》2015年第8期1365-1370,共6页Chinese Journal of Pathophysiology

基　　金：安徽省教育厅省级自然科学基金重点项目(No.KJ2011A265)

摘　　要：目的:观察钩藤碱对自发性高血压大鼠血压、心肌肥厚及心肌纤维化的影响并探讨其可能的作用机制。方法:32只自发性高血压大鼠随机分为模型组、钩藤碱高(10 mg·kg-1·d-1)、低(2.5 mg·kg-1·d-1)剂量组、卡托普利组(17.5 mg·kg-1·d-1),每组8只。另设8只Wistar-Kyoto大鼠作为正常对照组。分别于给药前和给药后每2周测量尾动脉收缩压(SBP)。治疗10周后处死大鼠,取其心脏计算全心重量指数和左心室重量指数;检测心肌中羟脯氨酸(HYP)及血浆中血管紧张素Ⅱ(AngⅡ)的含量;HE染色观察心肌病理学变化,Masson染色观察心肌胶原纤维变化;免疫组化法和Western blot法测心肌组织转化生长因子-β1(TGF-β1)和Smad3蛋白的表达。结果:与模型组相比,钩藤碱能明显降低自发性高血压大鼠的血压(P<0.05),降低心肌HYP含量及血浆AngⅡ的含量(P<0.05),减轻心肌组织的病理损伤和胶原纤维沉积,下调TGF-β1和Smad3蛋白的表达(P<0.01)。结论:钩藤碱能降低自发性高血压大鼠的血压、调节改善自发性高血压大鼠的心室重构,其机制可能与其影响TGF-β1/Smad通路以及降低AngⅡ含量有关。AIM： To investigate the effect of rhynchophylline（ Rhy） on blood pressure,cardiac hypertrophy and myocardial fibrosis in spontaneously hypertensive rats（ SHR）. METHODS： Spontaneously hypertensive rats were randomly divided into model group,high dose（ 10 mg·kg- 1·d- 1） and low dose（ 2. 5 mg·kg- 1·d- 1） group of rhynchophylline,captopril group（ 17. 5 mg·kg- 1·d- 1）. Wistar-Kyoto rats were used as normal control. Respectively,systolic blood pressure was measured by tail cuff every 2 weeks. After 10 weeks,heart weight index and left ventricular weight index were calculated. The myocardial hydroxyproline and plasma angiotensin Ⅱ were detected. Moreover,basic myocardial histopathological changes and myocardial collagen fibres were observed by HE staining and Masson staining,respectively.The protein expression of TGF-β1 and Smad3 in the myocardium was measured by the methods of immunohistochemistry and Western blot. RESULTS： Compared with SHR model group,Rhy significantly reduced blood pressure（P〈0. 05）,the levels of HYP in the myocardium（P〈0. 05） and the levels of AngⅡ in the plasma（P〈0. 01）. The pathological damages of the myocardial tissues and collagen deposition were attenuated. The protein expression of TGF-β1 and Smad3 was significantly reduced by the treatment with Rhy（P〈0. 01）. CONCLUSION： Rhynchophylline reduces blood pressure and adjusts to improve ventricular remodeling of SHR. The mechanism may be involved in the TGF-β1/ Smad pathway and reducing AngⅡ content.

关 键 词：钩藤碱 自发性高血压大鼠 TGF-β1/Smad通路 心室重构 

分 类 号：R363[医药卫生—病理学]