阻断肾素-血管紧张素系统对糖尿病大鼠肾脏血管紧张素ⅡAT1受体的影响

Effects of blocking renin-angiotensin system on expression of angiotensin Ⅱ type 1 receptors in the kidney of diabetic rats

目的:研究链脲佐菌素(STZ)诱导的早期糖尿病大鼠肾组织血管紧张素Ⅱ(AngⅡ)AT1受体的表达以及阻断肾素-血管紧张素系统(RAS)对其的影响。方法:糖尿病模型大鼠随机分为伊贝沙坦组、福辛普利组、两药合用组及糖尿病对照组,另设一正常对照组。采用放射免疫法检测各组血浆AngⅡ水平,免疫组织化学法及Western blot方法半定量检测肾组织中AT1受体的分布和表达。结果:糖尿病大鼠肾组织AT1受体表达较正常大鼠明显减弱,各用药组AT1受体表达较正常对照组明显上调。结论:糖尿病时肾脏局部RAS存在活性改变和重新分布。

Objective To investigate the expression of angiotensin Ⅱ （Ang Ⅱ ） type 1 （AT1） receptors in the kidney of diabetic rats and its effects of blocking renin-angiotensin system （RAS）. Methods Diabetic rats were given angiotensin Ⅱ receptor blocker, irbesartan （40 mg ·kg^- 1 ）, angiotensin-converting enzyme inhibitor, fosinopril （40 mg· kg^- 1 ）, and irbesartan plus fosinopril （20 mg· kg^- 1, respectively）, or placebo per day for 4 weeks. The expression of renal AT1 receptors were assessed by immunohistochemistry and Western blot. Results Immunoblot for AT1 receptors showed that the expression of AT1 receptors decreased significantly in diabetic kidney. Treatment with irbesartan, fosinopril and their combination significantly increased the expression of AT1 receptors compared with that of controls （ P 〈 0.05）. Conclusion In diabetes mellitus, treatment with irbesartan, fosinopfil and their combination changes the expression of AT1 receptors in renal cortex, suggesting that local RAS in diabetic kidney be actively involved in the pathogenesis of DN.