关键词：糖尿病；高血压；肾脏病变；一氧化氮
【摘要 】 目的 探讨糖尿病(DM)和高血压大鼠肾脏一氧化氮(NO)途径与DM肾病的关系。方法 将自发性高血压大鼠(SHR)制成链脲佐菌素(STZ)DM模型。设WKY、SHR和SHR-DM三组。除形态学观察外，还测定各组大鼠肌酐清除率(Ccr)、24小时尿蛋白、血及肾组织NO含量、肾脏NO合成酶(NOS)活性和NOSmRNA表达水平。结果 SHR-DM组大鼠24小时尿蛋白定量20周时明显高于其余两组，Ccr无明显改变。血NO水平升高，肾NO含量降低。肾脏结构型NOS(cNOS)活性下降，诱导型NOS(iNOS)活性或iNOS/cNOS(i/c)比值增加。肾小球NOSmRNA表达面积扩大，入球动脉及小叶间动脉NOS基因表达明显下降。肾小球系膜增生，有形成K-W结节或纤维蛋白帽的趋势，系膜区基质增多，基底膜增厚，肾小动脉壁厚腔窄。结论 (1)STZ-SHR-DM模型出现的24小时尿蛋白增加、肾小球系膜及肾小血管病变提示DM肾病的产生；(2)肾脏NO系统异常与DM肾病有关。
Role of nitric oxide on diabeticnephropathy
ZHENG Xu,LOU Jie,YANG Wenying,et al.Dptof endocrinology,Sino-Japanese Friendship Hospital,Beijing 100029
【Abstact 】 Objective Tostudy the relationship between nitric oxide(NO) pathway and diabetic nephropathy.Methods Ratswere randomly divided into WKY,SHR and SHR-DM which were treated with 75 mg/kg ofstreptozotocin(STZ) and maintained for 10 and 20 weeks respectively.Renal NO amount,NOsynthase(NOS) activity and NOS mRNA expression were measured besides morphologicalobservation.Results Glomerular lesions in SHR-DM group involvedmesangial cell proliferation trend of K-W node and fibrin cap,and accumulation ofmesangial matrix and thickness of glomerular membrane basement.There were still wallthickness and cavity stricture in renal resistant vasculature.In SHR-DM it existed lowerrenal NO level and constitutive NOS (cNOS) activity than WKY(P<0.01) and higherinducible NOS(iNOS) activity or iNOS/cNOS(i/c) ratio than both WKY and SHR(P<0.05).Thearea of NOS gene expression in glomeruli expanded(P<0.05)whereas NOS mRNA expression inafferent arterioles and interlobular arteries(at 20 week)reduced markedly in SHR-DM(P<0.01).Conclusion (1)thelesions of glomeruli and renal resistant vasculature caused by STZ-SHR-DM model confirmdevelopment of diabetic nephropathy in this study.(2)diabetic nephropathy is associatedwith abnormality of renal NO pathway.
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