西拉普利对糖尿病高血压大鼠肾脏内皮素系统的影响

目的　观察糖尿病高血压大鼠肾脏内皮素 (ET)系统的改变以及血管紧张素转换酶抑制剂 (ACEI)影响。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Cilazapril组、Amlodipine组和非治疗组。 4周后采用免疫组化和RT PCR方法检测肾脏ET 1及其A、B受体基因和蛋白表达。结果　与WKY对照组相比 ,SHR DM大鼠存在明显的蛋白尿和肾功能减退 ,肾脏ET 1及A受体的mRNA和蛋白表达也明显升高 ,而ETB受体的变化不显著 ,Cilazapril和Amlodipine治疗均可使肾脏ET 1降至正常水平 ,但仅Cilazapril能明显降低蛋白尿 ,改善内生肌酐清除率 ,下调ETA受体的过度表达。 结论　糖尿病高血压大鼠肾脏ET系统明显上调 ,Cilazapril较Amlodipine更具有治疗作用

Cilazapril Inhibits the Upregulated Endothelin System in the Kidney of Diabetic Hypertensive Rats

Purpose To investigate the changes of endothelin (ET) system in the kidney of spontaneously hypertensive rats (SHR) with diabetes and the influence of ACEI. Methods Streptozotocin induced diabetic SHR were divided into cilazapril treated group,amlodipine treated group,and untreated group.SHR and WKY rats were regarded as hypertensive and normotensive control group,respectively.The mean arterial blood pressure,urinary protein excretion,creatinine clearance,plasma and renal endothelin as well as renal expression of endothelin 1 and its receptors were determined at the end of 4th week. Results Both antihypertensive therapies attenuated the rise in blood pressure of untreated diabetic SHR.The enhanced urinary protein excretion and decreased creatinine clearance as well as increased plasma and renal endothelin levels were also observed in untreated diabetic SHR compared to WKY rats.Immunohistochemistry and RT?PCR method showed that the amount of protein and mRNA expression of ET?1 and type A receptor in the kidney were significantly increased in untreated diabetic SHR compared with those in WKY rats.However,endothelin type B type receptor expression were not altered in the kidney from all groups.All these abnormalities were obviously ameliorated by cilazapril. Conclusions Cilazapril could effectively inhibit the upregulated ET system in the kidney of diabetic SHR.