内皮素受体阻断剂对糖尿病大鼠肾脏血管紧张素Ⅱ1型受体表达的影响

目的：观察糖尿病大鼠肾脏血管紧张素Ⅱ1型（AT1）受体的改变以及内皮素受体阻断剂bosentan对其影响。方法：将SD大鼠建成链脲佐菌素诱导的糖尿病模型,设非治疗组、bosentan治疗组和正常对照组。4周后采用免疫组织化学、Western blot及RT－PCR方法检测肾脏AT1受体基因和蛋白表达。结果：与SD对照组相比,糖尿病大鼠存在明显的蛋白尿和内生肌酐清除率升高,其肾脏AngⅡ水平明显升高,同时伴有AT1受体的mRNA和蛋白表达显著下降。bosentan能显著缓解上述异常。结论：糖尿病大鼠肾脏AngⅡ及AT1受体表达明显异常,bosentan具有治疗作用。

Effect of endothelin blockade on expression of angiotensin II type 1 receptor in the kidney of diabeticrats

Objective To investigate whether the renal expression of angiotensin II(Ang II) type 1 (AT1) receptor is affected by endothelin receptor antagonist bosentan in diabetic rats. Methods Male SD rats(8-week old) were divided into three groups: streptozotocin-induced diabetic rats, bosentan-treated diabetic rats, and control non-diabetic rats. Creatinine clearance, urinary protein excretion, mean arterial blood pressure ,renal endothelin and AngII levels as well as renal AT1 receptor expression were determined at 4th week. Results Bosentan attenuated the rise in creatinine clearance and reduced urinary protein excretion in diabetic rats, but did not affect blood pressure. Both renal endothelin and AngII levels were significantly increased in diabetic rats compared to control rats. The latter abnormality was also ameliorated by bosentan. Semi-quantitative RT-PCR, immunohistochemistry and Western blot analysis showed that bosentan attenuated the decreased mRNA and protein levels of ATI receptor in the kidney of diabetic rats. Conclusion Bosentan may be used in the treatment of diabetic nephropathy by ameliorate the disorders of AngII and AT1 receptor in the kidney.