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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 observe the renal protective effects of bosentan on diabetic hypertensive rats. Methods Spontaneous hypertensive rats were induced with streptozotocin-induced diabetes mellitus (SHR-DM). The bosentan + amlodipine group, the amlodipine group, the cilazapril group and the untreated group were established. After 4 weeks, the changes of extracellular matrix and transforming growth factor-β1 (TGFβ1) were observed by immunohistochemistry and Western blot. Results Compared with WKY rats, the urinary albumin excretion, creatinine clearance rate and the expressions of type Ⅳ collagen, laminin and TGFβ1 in SHR-DM rats increased significantly at 24 hours. bosentan + amlodipine treatment can significantly alleviate the above abnormalities, the effect is similar to cilazapril group. Conclusions Bosentan combined with amlodipine can delay renal damage in patients with diabetes mellitus.