血管内皮生长因子及其受体对糖尿病肾病大鼠微血管病变的作用

目的：探讨血管内皮生长因子（VEGF）及其受体（VEGFR2）在糖尿病肾病（DN）大鼠肾微血管病变发病中的作用。方法：将正常Wistar大鼠12只随机分为正常对照组、糖尿病肾病组。糖尿病肾病组用STZ诱导建立DN模型,大鼠自由进食、饮水。于第4周和第8周各组分别处死大鼠6只。测定血生化及24h尿蛋白定量,以正常肾小球为对照,采用特异性抗体和免疫组织化学方法,观察大鼠肾小球VEGF、VEGFR2、TM-1的分布及其强度变化,并结合肾脏病理进行分析。应用RT-PCR技术测定VEGF和VEGFR2mRNA的表达。结果：（1）糖尿病肾病组第4周,8周时,尿白蛋白排泄率,血糖,血脂升高,均高于正常对照组（P〈0.01）,肾组织光镜,出现早期糖尿病肾病典型的病理改变过程。（2）免疫组化显示糖尿病组4周、8周时肾脏VEGF、VEGFR2及TM-1表达均较正常对照组上调（P〈0.01）,VEGF与TM-1呈正相关（4周时r=0.947,P〈0.001;8周时r=0.923,P〈0.001）;RT-PCR检测结果显示糖尿病肾病组第8周时VEGF-mRNA和VEGFR2-mRNA表达均较正常对照组升高（P〈0.05）,第8周时VEGF-mRNA和VEGFR2-mRNA表达较第4周时增高（P〈0.05）。结论：糖尿病肾病大鼠肾小球VEGF、VEGFR2、TM-1表达增强,与糖尿病肾脏新生血管生成有关。

The Effects of Vascular Endothelial Growth Factor and its Receptor on the diabetic nephropathy in rats

Objective：To investigate the expressions of vascular endothelial growth factor（VEGF）and its receptor（VEGFR2）in the kidney of the Streptozotocin-induced diabetic nephropathy rats.Methods：24 healthy Wistar rats were equally divided into two groups at random：control group and diabetic nephropathy group.The diabete nephropathy group was made into Streptozotocin-induced diabetic nephropathy models.The control group and diabetic nephropathy group were treated by corresponded tap water.4 weeks and 8 weeks later,half rats of each group was killed.We measured serum biochemical indicator and protein amountof 24 hours urine.Differential antibody methods and immunohistochemistrywere performed to determine the protein expression of VEGF、its receptor-VEGFR2 and TM-1.Results：（1）It was found that there was an increasing in both of the distribution and staining intensity of VEGF、VEGFR2 and TM-1 in diabetic nephropathy group as compared with control group（P0.01）.（2）VEGF and TM-1 were in obviously positive correlation（4wk,r=0.947,P0.001;8wk,r=0.923,P0.001）.（3）The same trend was existed with the expressions of VEGF and VEGFR2 mRNA.（P0.05）.Conclusion：The protein expressions of VEGF、VEGFR2 and TM-1 were significantly increased in the diabetic nephropathy rats.And its may be relevant to the increasing number of new vessels.