中华医学杂志（英文版）2002，Vol.115Issue(7)：972-978,7.
内皮素受体阻断剂合用钙通道阻滞剂能抑制糖尿病高血压大鼠的肾脏损害
Endothelin receptor antagonist combined with a calcium channel blocker attenuates renal injury in spontaneous hypertensive rats with diabetes
摘要
Abstract
Objective To investigate the effects of the mixed endothelin receptor antagonist, bosentan, combined with the long-acting calcium channel blocker, amlodipine, compared to the angiotensin-converting enzyme inhibitor, cilazapril, on the progressive renal injury in spontaneous hypertensive rats (SHR) with diabetes.Methods Diabetic hypertensive rats (SHR-DM) were induced by streptozotozin injected in male SHR (7-week-old), and divided into an untreated and three treated groups: ① cilazapril treated group; ② bosentan+amlodipine treated group; and ③ amlodipine treated group. Wistar Kyoto rats (WKY) and SHR rats served as normotensive and hypertensive control, respectively. The mean arterial blood pressure, renal function, endothelin and angiotensin Ⅱ levels as well as the protein expression of renal extracellular matrix components and transforming growth factor (TGF)-β1 were determined at the end of the 4th week.Results Mean arterial blood pressure significantly increased in SHR and SHR-DM rats compared to WKY rats. All the therapies reduced the blood pressure to normal levels. However, the enhanced urinary protein excretion, the decreased creatinine clearance as well as the increased plasma and intrarenal endothelin and angiotensin Ⅱ levels were found in the untreated SHR-DM and prevented by treatment with bosentan+amlodipine and cilazapril. Similarly, these two kinds of therapies in SHR-DM abolished the overexpression of renal TGF-β1 by Western blot analysis and reduced the accumulation of collagen type Ⅳ, laminin and fibronectin proteins by an immunochemical approach. Amlodipine monotherapy had no detectable effects on the above parameters.Conclusion Bosentan combined with amlodipine can offer similar renoprotective effects on that of cilazapril and may be a potent therapy to attenuate renal injury by reducing renal protein levels of TGF-β1 in diabetes with a hypertensive state.关键词
肾脏损害/高血压/糖尿病/内皮素受体阻断剂Key words
renal injury/hypertension/diabetics/endothelin receptor antagonist分类
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陈靖,顾勇,林凡,杨海春,朱蔚钰,马骥,林善锬..内皮素受体阻断剂合用钙通道阻滞剂能抑制糖尿病高血压大鼠的肾脏损害[J].中华医学杂志（英文版）,2002,115(7):972-978,7.基金项目
This research work was supported by Ministry of Public Health and Shanghai Bairen Project Foundation (No. 98BR038). （No. 98BR038）
