摘要
目的探讨缬沙坦对2型糖尿病大鼠(T2DM)肾脏骨桥蛋白(OPN)和骨形态发生蛋白-7(BMP-7)表达的影响。方法 Wistar大鼠随机分为3组:对照组、DM模型组和缬沙坦治疗组[25mg/(kg·d)]。高脂、高糖喂养联合小剂量链脲佐菌素建立T2DM模型。缬沙坦治疗12周末,测定血压、血糖、尿白蛋白(UAL)排泄量;应用光镜观察肾脏病理变化;采用免疫组化、实时定量PCR技术测定肾组织BMP-7、OPN、转化生长因子-β_1(TGF-β_1)蛋白及mRNA的表达。结果与对照组比较,DM组大鼠UAL及肾组织ED-1阳性细胞数明显升高(P<0.01);肾组织BMP-7mRNA及蛋白的表达下调(P<0.01),而OPN、纤连蛋白及TGF-β-1的表达显著上调(P<0.01)。缬沙坦干预后明显减少UAL的排泄(P<0.01),并显著抑制肾组织巨噬细胞浸润及TGF-β_1、OPN和纤连蛋白过度表达(P<0.05),同时上调BMP-7的表达(P<0.01)。结论缬沙坦减少肾组织巨噬细胞浸润及细胞外基质,对糖尿病性肾病有保护作用,其机制可能与下调TGF-β_1和OPN及恢复BMP-7的表达有关。
Objective To investigate the effect of valsartan on osteopontin（OPN） and bone morphogenetic protein-7 （BMP-7） in the kidneys of type 2 diabetic mellitus （T2DM） rats. Methods Wistar rats were divided into control, T2DM, and valsartan treatment [25 mg/（kg · d）] groups. Rats were fed high sucrose high fat diet combined with a low dose of streptozotocin （STZ） to induce T2DM models. After administration of valsartan for 12 weeks, blood pressure, blood glucose, urinary albumin （UAL） and creatinine clearance （CCr） were determined. Renal morphology was observed under light microscope. The protein and mRNA expressions of BMP-7, OPN, transforming growth factor-β1 （TGF-β1）, fibronectin and ED-1 in renal tissue were determined by immunohistochemistry and quantitative real time PCR respectively. Results Compared with control group, in T2DM rats, UAL was significantly increased （P〈0.01）; the expressions of BMP-7 protein and mRNA were significantly decreased （P〈0.01）; the expressions of OPN, fibronectin and TGF-β1 were elevated （P〈0.01）. UAL was markedly attenuated by valsartan （P〈0.01）. Valsartan effectively suppressed the expressions of fibronectin, OPN and TGF-β1 and decreased ED-1 positive cells （P〈0.05）, while significantly upregulated the expressions of BMP-7 （P〈0.01）. Conclusion Valsartan has protective effects on diabetic nephropathy by decreasing macrophage infiltration and reducing extracellular matrix accumulation, which may involve the down regulation of TGF-β1 and OPN, as well as recovery of BMP-7.
出处
《中华老年多器官疾病杂志》
2011年第1期60-65,共6页
Chinese Journal of Multiple Organ Diseases in the Elderly
基金
青岛市科技局课题(2005市科委-24)~~
