VEGF、TGF-β1在糖尿病肾小管表达的实验研究

目的:探讨糖尿病(DM)大鼠肾小管血管内皮生长因子(VEGF)、转化生长因子β1(TGF-β1)、血管紧张素Ⅱ(AngⅡ)的表达与糖尿病肾病(DN)发生发展的关系。方法:尾静脉注射链脲佐菌素(STZ)建立糖尿病模型,分为DM 3 d、1周、2周、4周、8周组及相应正常对照组;免疫组织化学法检测VEGF、TGF-β1、AngⅡ、FN(纤维连接蛋白)在肾小管的表达;Western免疫印记法检测肾皮质VEGF蛋白质水平;PAS染色光镜观察肾组织形态改变。结果:肾皮质VEGF水平随病程发展表达逐渐增多,免疫组化示肾小管VEGF在DM 1周时显著高于对照组,且在4周时与24 h尿蛋白量呈正相关;DM大鼠肾小管AngⅡ、TGF-β1表达显著高于正常组,在DM 4周与VEGF呈正相关且三者均与FN呈正相关性。结论:DM大鼠肾小管VEGF表达上调,可能介导DN蛋白尿的产生;AngⅡ、TGF-β1可能同VEGF一起共同参与糖尿病肾脏纤维化过程。

Experimental study on expression of VEGF and TGF-β1 in renal tubules of diabetic rats

Objective:To explore the relationship between the expression of VEGF,AngⅡ,TGF-β1 in renal tubules of streptozotocin-induced dia- betic rats and the development of diabetic nephropathy.Methods:Dia- betic rat models were induced by injecting streptozotocin through vena caudalis and the animals were randomly divided into group of 3 days,1 week,2 weeks,4 weeks and 8 weeks and corresponding controls.The expression of VEGF,AngⅡ,TGF-β1 and fibronectin in renal tubules were determined by immunohistochemistry.Western blotting was used to detect the expression of VEGF protein in renal cortex,and the mor- pholngical changes of renal tissues were checked through microscopy by PAS staining.Results:With the advancement of diabetes,the level of VEGF in renal cortex was increased.The expression of VEGF was in- creased in model group of 1 week,which had positive relation with 24h urine protein.The expression of TGF-β1 and AngⅡin renal tubules of diabetic groups was increased remarkably compared with that of corre- sponding control groups and was correlated with VEGF.The expression of VEGF,TGF-β1 and AngⅡwas positively correlative with that of fi- bronectin in tbe 4th week.Conclusion:The increased expression of VEGF in renal tubules of diabetic rats may promote the occurrence of al- buminuria.Angβ,TGF-β1 and VEGF may play an important role in the fibrosis of the diabetic nephropathy.