糖尿病鼠肾小管周围新生血管与促血管生长因子关系研究

目的探讨促血管生成素-2(Ang-2)和血管内皮生长因子(VEGF)在糖尿病肾脏血管新生中的作用及其意义。方法2004年3月至2005年3月在四川大学华西医院用SD大鼠建立链唑霉素(STZ)诱导的糖尿病肾病模型,定量分析肾脏VEGF和Ang-2的表达变化,用逆转录聚合酶链式反应技术(RT-PCR)检测肾脏VEGF、Ang-2的mRNA的表达。结果糖尿病组肾脏VEGFmRNA表达从2周开始持续上调,16～20周达高峰;免疫组化显示糖尿病组各时点肾小管的VEGF着染均强于对照组;糖尿病组仅于16周和20周时探及肾组织Ang-2mRNA表达,12～24周免疫组化显示皮质区管周Ang-2着染管周微血管,整个实验期间对照组未探及Ang-2mRNA和蛋白表达;VEGF与Ang-2的改变呈正相关。结论糖尿病肾脏中后期皮质区存在Ang-2着染的新生管周微血管,VEGF与Ang-2参与糖尿病肾脏新生血管生成。

The experimental study on the relationship between proangiogenic factors and the peritubular angiogenesis of diabetic renal

Objective To explore the role and significance of vascular endothelial growth factor(VEGF)and angiopoietin-2(Ang-2)in peritubular angiogenesis of diabetic kidney.Methods diabetic rats were induced by Streptozotocin.The expressions of VEGF and Ang-2 in renal tissue of rats were detected by immunohisochemistry.VEGF and Ang-2 mRNA in kidney was also detected by RT-PCR,and quantified by computerimage analysis.Results From 2-week to 24-week,VEGF mRNA level in diabetic renal upregulated continuously compared with control group,with peak level at 16 and 20 weeks.VEGF immunostaining in diabetic renal tubuli increased apparently compared with control group.Ang-2 mRNA in diabetic renal was only detected at 16 and 20 weeks.Ang-2-expressing peritubular microvessel in diabetic renal cortex was found by immunohistochemistry from 12 -week to 24-week with peak level at 16 week.No detecable Ang-2 mRNA and immunostaining were found in control renal.The changes correlated VEGF with Ang-2 in diabetic renal after 12 weeks.Conclusion There are the formation of Ang-2-staining peritubular microvessels in diabetic renal cortex in middle and later stages.VEGF and Ang-2 take part in angiogenesis in diabetic renal.