转化生长因子β_1在单侧肾切除糖尿病大鼠肾皮质中表达  

The expression of transforming growth factor β_1 in renal cortex from uninephrectomized diabetic rats

作　　者：吴永贵[1] 林善锬[1] 余毅 黄宇峰[1] 周江华[1] 

机构地区：[1]上海医科大学附属华山医院肾内科,200040 [2]福州军区总医院肾内科

出　　处：《中华肾脏病杂志》1998年第5期301-306,共6页Chinese Journal of Nephrology

基　　金：美国中华医学基金

摘　　要：目的研究转化生长因子β1(TGFβ1)在单侧肾切除糖尿病大鼠肾皮质中表达。方法将Wistar大鼠随机分成单侧肾切除A组和单侧肾切除糖尿病B组,观察STZ注射一、四周后血糖、血胰岛素水平、体重、肾重、肾重/体重及肾组织蛋白含量变化。利用Northern杂交检测肾皮质TGFβ_、1α(Ⅳ)前胶原及纤维连接蛋白(FN)mRNA表达,Western杂交检测TGFβ_1蛋白水平。另外,使用荧光分光度法测定血浆、肾皮、髓质血管紧张素转换酶(ACE)活性变化。结果 B组血糖进行性升高,血胰岛素水平逐渐下降,尽管体重逐渐下降,肾重、肾重/体重及肾组织蛋白含量却逐渐增加,四周末与A组相比有显著性差别(P<0.05)。Northern杂交表明B组肾皮质内TGFβ_1表达明显增加,一、四周分别升高1.75和3.94倍(P<0.05),同时1α(Ⅳ)前胶原及FN mRNA表达也进行性增加,Western杂交显示B组TGFβ_1蛋白表达在一、四周分别升高0.95倍和2.1倍。虽然B组血浆ACE活性有下降趋势,但肾皮质内ACE活性却逐渐升高,四周有显著意义(P<0.05)。结论糖尿病状态下肾皮质TGFβ_1,表达进行性增加是肾脏肥大的重要因素之一,局部肾素-血管紧张素(RAS)系统异常可能参与其发病过程。Objective To investigate the expression of transforming growth factor β_1(TGFβ_1)in renal cortex from uninephrectomized diabetic rats. Methods Wistar rats were divided into uninephrectomized rats(group A), streptozotocin diabetic rat(group B). Blood glucose, serum insulin level and body weight, kidney weight, kidney weight/body weight as well as renal tissue protein contents were observed after 1, 4 weeks of streptozotocin injection. The expression of TGFβ_1, precollagen 1α(Ⅳ) and fibronectin mRNA were measured by Northern blot analysis, and TGFβ_1 protein by Western blot analysis in kidney cortex. In addition, ACE activities were determined by fluorimetric assay in plasma, kidney cortex and medulla. Results Group B demonstrated significantly elevated blood glucose and decreased serum insulin level. Kidney weight、kidney weight/body weight and renal tissue protein contents progressively increased despite total body weight loss. There was significant(P<0.05)difference between two groups after 4 weeks. Northern blot analysis showed markedly enhanced(P<0.05) TGFβ_1 mRNA expression by 1.74, 3.94 fold after 1、4weeks in renal cortex, meanwhile, the mRNA expressions of precollagen 1α(Ⅳ)and FN were also increased. Western blot analysis demonstrated elevated TGFβ_1 protein expression by 0.9, 2.1fold after 1、4 weeks in renal cortex. Renal cortex ACE activity significantly increased despite decreased ACE activity in plasma after 4 weeks. Conclusion The early kidney hypertrophy and increased matrix mRNA are largely modulated by increased TGFβ_1 expression, probably caused by high blood glucose and locally increased ACE activity in kidney cortex.

关 键 词：糖尿病 TGFΒ1 肾切除 肾皮质 

分 类 号：R587.1[医药卫生—内分泌]