内皮素阻断对糖尿病高血压大鼠肾脏AT1受体表达的影响

目的 观察糖尿病高血压大鼠肾脏AT1受体的改变以及内皮素受体阻断剂波生坦的影响。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）,设柳平舒组、波生坦＋氨氯地平（络活喜）组、络活喜组和非治疗组,4 一采用免疫组织化学、Western印迹法及逆转录－聚合酶链式反应（RT－PCR）方法检测肾脏AT1受体基因和蛋白表达。结果 与WKY大鼠对照组相比,SHR－DM大鼠存在明显的蛋白尿和肾功能减退,肾脏AngⅡ水平明显升高,ＡＴ１受体的mRNA和蛋白表达则显著下降。波生坦能使上述异常显著减轻。结论 糖尿病高血压大鼠肾脏ＡＴ１受体表达明显下调;波生坦可减轻ＳＨＲ－ＤＭ大鼠肾脏损害并防止ＡＴ１受体表达下调。

The effects of endothelin blockade on renal expression of angiotensin II type 1 receptor in diabetic hypertensive rats

OBJECTIVE: To investigate the changes of angiotensin II type 1 (AT1) receptor in the kidney of spontaneously hypertensive rats (SHR) with diabetes and the influence of endothelin receptor antagonist bosentan. METHODS: Streptozotocin-induced diabetic SHR were divided into four groups: groups treated by cilazapril, bosentan + amlodipine, and amlodipine rsspectively, and untreated group, 6 rats in each group. Six SHR rats and six WKY rats were used as hypertensive and normotensive controls respectively. By the end of the 4th week, all rats were anasthetized and catheteization was conducted to their right common carotis arteries to measure the mean arterial blood pressure and collect blood samples to determine the blood sugar and creatinine by biochemical analyzer, and plasma angiotensin II level by radioimmunoassay. Then the rats were killed and their kidneys were taken. The renal angiotensin II (Ang II) receptor and expression of AT1 receptor was determined by RT-PCR and Western blotting. One day before the rats were killed, 24-hour urine was collected to determine the urinary protein and creatinine. RESULTS: In untreated diabetic SHR, enhanced blood pressure and urinary protein excretion, reduced creatinine clearance, as well as significantly increased plasma and renal Ang II levels were observed compared with those in WKY rats. Immunohistochemistry, Western blotting and semi-quantitatively RT-PCR methods showed that the protein and mRNA levels of AT1 receptor in kidney were significantly reduced in untreated diabetic SHR compared to those in WKY rats. All these abnormalities were attenuated by bosentan + amlodipine and cilazapril therapies. CONCLUSION: Bosentan prevents the down-regulation of AT1 receptor in the kidneys of diabetic hypertensive rats.