波生坦对糖尿病高血压大鼠肾脏的保护作用  

Renoprotective effects of endothelin receptor antagonist bosentan on diabetic hypertensive rats

作　　者：陈靖[1] 顾勇[1] 杨海春 朱春晓 朱蔚钰 林凡[2] 林善锬[1] 

机构地区：[1]上海医科大学华山医院肾病科,200040 [2]温州医学院第一附属医院肾病科

出　　处：《中华肾脏病杂志》2000年第2期71-75,共5页Chinese Journal of Nephrology

基　　金：国家自然科学基金!39470335;上海市"百人计划"基金

摘　　要：目的观察内皮素受体阻断剂（bosentan）对糖尿病高血压大鼠的肾脏保护作用。方法将自发性高血压大鼠建成链脲佐菌素诱导的糖尿病模型（SHR－DM），设bosentan＋氨氯地平（amlodipine）组、amlodipine组、西拉普利（cilazapril）组和非治疗组。4周后采用免疫组织化学和Westernblot方法观察肾脏细胞外基质和转化生长因子β1（TGFβ1）的改变。结果与WKY大鼠对照组相比，SHR－DM大鼠24小时尿蛋白排出量增加，肌酐清除率下降，肾内Ⅳ型胶原、laminin和TGFβ1蛋白表达明显升高。bosentan＋amlodipine治疗可显著缓解上述异常，疗效与cilazapril组相似。结论糖尿病高血压时，bosentan合用amlodipine可以延缓肾脏损害。Objective To investigate the effects of endothelin receptor antagonist bosentan on the progression of renal injury in spontaneously hypertensive rats (SHR) with diabetes. Methods Streptozotocin-induced diabetic SHR were divided into bosentan + amlodipine group, amlodipine group,cilazapril group, and untreated group. The protein expressions of renal matrix proteins and transforming growth factor (TGF) β1 were determined by immunohistochemistry and Western blot analysis at 4th week.Results Enhancedurinary protein excretion, decreased creatinine clearance, and over-expressions of type Ⅳ collagen, laminine and TGFβ1 were observed in untreated diabetic SHR compared with those in WKY group. All these abnormalities were ameliorated by bosentan + amlodipine, as effectively as cilazapril. Concusion The combination of bosentan with amlodipine may provide a new therapeutic approach to attenuate renal damage in diabetes with hypertensive state.

关 键 词：糖尿病 高血压 波生坦 肾脏 保护作用 

分 类 号：R587.1[医药卫生—内分泌]