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

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

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。

Objective To explore the role and significance of vascular endothelial growth factor （VEGF） and angiopoi- etin -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 per/tubular 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 per/tubular microvessels in diabetic renal cortex in middle and later stages. VEGF and Ang - 2 take part in angiogenesis in diabetic renal.