一氧化氮在糖尿病肾病中的作用

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 diabetic nephropathy

Objective To study the relationship between nitric oxide(NO) pathway and diabetic nephropathy. Methods Rats were randomly divided into WKY,SHR and SHRDM which were treated with 75 mg/kg of streptozotocin(STZ) and maintained for 10 and 20 weeks respectively.Renal NO amount,NO synthase(NOS) activity and NOS mRNA expression were measured besides morphological observation. Results Glomerular lesions in SHRDM group involved mesangial cell proliferation trend of KW node and fibrin cap,and accumulation of mesangial matrix and thickness of glomerular membrane basement.There were still wall thickness and cavity stricture in renal resistant vasculature.In SHRDM it existed lower renal NO level and constitutive NOS (cNOS) activity than WKY(P<001) and higher inducible NOS(iNOS) activity or iNOS/cNOS(i/c) ratio than both WKY and SHR(P<005).The area of NOS gene expression in glomeruli expanded(P<005)whereas NOS mRNA expression in afferent arterioles and interlobular arteries(at 20 week)reduced markedly in SHRDM(P<001). Conclusion (1)the lesions of glomeruli and renal resistant vasculature caused by STZSHRDM model confirm development of diabetic nephropathy in this study.(2)diabetic nephropathy is associated with abnormality of renal NO pathway.