【摘要】 目的探讨血管紧张素受体拮抗剂缬沙坦对糖尿病大鼠肾脏病变的保护作用及其机制。方法将实验动物分为正常对照组、糖尿病组及缬沙坦治疗组。检测各组第２、４、８周的平均动脉压、血糖、血胰岛素、血肌酐、尿白蛋白、肾组织血管紧张素转换酶（ＡＣＥ）活性、血管紧张素Ⅱ（ＡｎｇⅡ）含量及肾脏肥大指标的变化，应用Ｎｏｒｔｈｅｒｎ杂交检测肾皮质中转化生长因子β１（ＴＧＦβ１）ｍＲＮＡ表达，免疫组化检测肾内ＴＧＦβ１，纤维连接蛋白（ＦＮ）和Ⅳ型胶原蛋白表达水平。结果缬沙坦治疗组较糖尿病非治疗组尿白蛋白排泄量明显减少（Ｐ＜００１），血肌酐水平下降（Ｐ＜００５），肾脏肥大指标改善（Ｐ＜００５）。Ｎｏｒｔｈｅｒｎ杂交表明糖尿病大鼠肾皮质ＴＧＦβ１ｍＲＮＡ表达进行性升高，免疫组化显示肾小管上皮细胞ＴＧＦβ１蛋白表达增多，肾小球ＦＮ和Ⅳ型胶原沉积增多，缬沙坦治疗组ＴＧＦβ１基因（Ｐ＜００１）和蛋白（Ｐ＜００５）表达均明显低于非治疗组，治疗８周后ＦＮ和Ⅳ型胶原蛋白表达低于非治疗组（Ｐ＜００５）。结论缬沙坦对糖尿病肾脏病变有部分保护作用，其机制可能是通过下调糖尿病大鼠ＴＧＦβ１的表达，减少细胞外基质的沉积。更多还原

【Abstract】 Objective To investigate the machenism of valsartan in protecting the renal lesion of diabetic rats. Methods The following groups of rats were studied: normal control rats, streptozotocin diabetic rats and diabetic rats treated with valsartan (8 mg·kg -1 ·d -1 ). Mean arterial pressure, plasma glucose, serum insulin, serum creatinine, urinary albumin, ACE activity and Ang Ⅱ concentration of kidney as well as profile of kidney hypertrophy were observed after 2, 4, 8 weeks of treatment, while TGFβ 1 mRNA expression of kidney cortex was assessed by Northern blot analysis, TGFβ 1, fibronectin and collagen Ⅳ expression were measured by immunohistochemistry. Results Serum creatinine level ( P <0.05), urinary albumin excretion and kidney hypertrophy index ( P <0 01) of valsartan treated group were significantly lower than those of diabetic untreated group. There was a significant increase in mRNA expression of TGFβ 1 and protein expression of of TGFβ 1 fibronectin and collagen Ⅳ in diabetic rats ( P <0.01). The expression of TGFβ 1 mRNA and protein ( P <0.01) as well as the protein expression of fibronectin and collagen Ⅳ ( P <0.05) in the valsartan group were much lower than that in the diabetic group. Conclusion The results suggested that valsartan has some renal protective effect on diabetes in rats, partly through down regulating TGFβ 1 expression and reducing deposition of glomerular ECM.更多还原