摘要
目的 :观察氯沙坦对链脲佐菌素 (STZ)诱导的糖尿病大鼠肾脏转化生长因子 β1(TGF β1)和细胞外基质 (ECM )%DⅣ型胶原、纤维连接蛋白 (FN)表达的影响 ,以探讨糖尿病早期肾脏肥大和氯沙坦对糖尿病肾病 (diabetesnephropathy ,DN)保护作用的可能机理。方法 :实验大鼠随机分为 3组 ,每组 12只 :正常对照组 (C组 )、糖尿病组 (D组 )和氯沙坦治疗组 (DL组 )。左下腹腔注射STZ 6 0mg/kg体重制成糖尿病模型 ,DL组在糖尿病模型确立后第 2d予氯沙坦 10mg/(kg .d)灌胃 ,C组与D组仅给予等量自来水灌胃。检测各组第 4、 8wk末 (每组各取 6只 )的血糖、尿白蛋白、血浆血管紧张素Ⅱ含量及相对肾重 ;免疫组化检测肾内TGF β1、FN和Ⅳ型胶原蛋白表达水平 ,图像分析系统分析光密度值。结果 :DL组较D组尿白蛋白排泄量明显减少 ,相对肾重减轻 (P <0 0 1) ;免疫组化显示糖尿病大鼠肾内TGF β1蛋白表达增多 ,肾小球FN和Ⅳ型胶原沉积增多 ;DL组TGF β1蛋白表达均明显低于D组 ,治疗 8wk后FN和Ⅳ型胶原蛋白表达低于D组 (P <0 0 5 )。结论 :肾脏ECM积聚是糖尿病肾脏肥大的重要原因 ;氯沙坦对糖尿病肾脏病变的保护作用机制可能部分是通过下调糖尿病大鼠肾脏的TGF β1表达 。
Objective: To investigate the influence of losartan on expression of transforming growth factor-β 1 and extracellular matrix components in the glomeruli of diabetes rats. Methods: 36 rats were randomized into three groups : normal control group (group C, n=12) , streptozotocin diabetic group (group D, n=12) and the group of diabetic rats treated with losartan(group DL, n=12, 10mg·kg -1·d -1 of losartan injected into left-lower part of abdominal cavity since the 2 nd day of streptozotocin injection). Blood glucose、urinary albumin、 plasma Angiotensin Ⅱ concentration as well as profile of kidney hypertrophy were observed after 4、 8 weeks of treatment , while TGF-β 1 , fibronection and collagen Ⅳ expression were measured by immunohistochemistry. Results:Urinary albumin excretion and kidney hypertrophy index of losartan treated group were significantly lower than those of diabetic untreated group (P<0.01 ). There was a significant increase in protein expression of TGF-β 1, fibronection and collagen Ⅳ in diabetic rats (P<0.01 ) . The expression of TGF-β 1 (P<0.01 ) protein as well as the protein expression of fibronection and collagen Ⅳin the losartan group were much lower than that in the diabetic group (P<0.05 ). Conclusion: The results suggest that losartan has some renal protective effect on diabetes in rats , partly by down-regulating TGF-β 1 expression and reducing deposition of glomerular ECM .
出处
《湖北省卫生职工医学院学报》
2004年第3期1-4,共4页
Journal of Hubei Medical Staff College
关键词
氯沙坦
糖尿病肾病
转化生长因子Β
细胞外基质
受体
血管紧张素
Losartan
Diabetes nephropathy
Transforming growth factor beta
Extracellular matrix
Receptor
Angiotensin
