血管生成素1和血栓调节蛋白1在STZ鼠肾脏中的表达及其意义

目的：探讨血管生成素1（angiopoietin-1,Ang-1）和血栓调节蛋白1（thrombomodulin-1,TM-1）在糖尿病鼠肾脏中的表达变化及其与肾脏微血管病变的关系. 方法：STZ诱导的糖尿病大鼠肾病模型,设正常对照和模型组,于2、4、8、12、16、20、24周,采用免疫组化观察肾脏Ang-1和TM-1表达变化以及RT-PCR观察肾脏Ang-1mRNA表达,并行相关性分析. 结果：糖尿病组4和8周时肾脏Ang-1mRNA表达显著上调, 24周时明显低于对照组;糖尿病组4～24周免疫组化显示肾小球Ang-1着染均显著高于对照组,峰值在4～8周,12周后逐渐下调;糖尿病组2～20周肾小球TM-1明显增强;Ang-1和TM-1呈正相关. 结论：糖尿病肾脏存在Ang-1和TM-1的异常改变,表现为早中期表达上调,后期表达下调,并且这种改变可能与糖尿病肾脏新生血管的生成有关.

The expression of the angiopoietin-1 and thrombomodulin-1 in the kidney of diabetic rats

Objective:To investigate the expression of angiopoietin-1 (Ang-1) and thrombomodulin-1 (TM-1) on renal tissue in diabetic rats, and explore that those changes are whether or not correlated to the diabetic angiogenesis. Methodology:Eighty-four, male and weight from 150 to 200g, SD rats were divided two groups. They were streptozotocin (STZ, 50mg/kg, peritoneal injection)-induced diabetic group and normal control group. The expressions of Ang-1 and TM-1 in renal were detected by immunohisochemistry at 2, 4, 8, 12, 16, 20 and 24 weeks both in two groups. Ang-1 mRNA was detected by RT-PCR at the same time-points. The levels of Ang-1 and TM-1 were quantified by computer image analysis. Results:Ang-1 mRNA on renal tissue in rats with diabetes was significantly upregulated at 4 and 8 weeks compared with that in diabetic group at other time points or in control group at the same time-points, while decreased evidently at 24 week compared with that in control group. From 4-week to 24-week, Ang-1 was outstandingly expressed on glomeruli in rats with diabetes, the number of Ang-1 staining in diabetic glomeruli increased significantly compared with that in control group, being maximal at 4 and 8 weeks, and subsequently decreased after 12 week. The level of TM-1 on renal tissue in diabetic rats was increased significantly compared with that in control group at the same time-points. It was found that there was a strong correlation between Ang-1 and TM-1. Conclusion:The expression of Ang-1 and TM-1 on renal tissue in rats with diabetes is exchanged, which are early upregulation and later downregulation,. Those changes are correlated with renal angiogenesis.