Ang-2和TM-1与糖尿病鼠肾新生血管生成关系的初步研究

目的：探讨糖尿病肾脏促血管生成素-2（angiopoietin-2,Ang-2）和血栓调节蛋白（thrombomodulin-1,TM-1）表达变化及其与新生血管生成的关系。方法：用雄性SD大鼠建立STZ诱导的糖尿病肾病模型,设正常对照和模型组,分别于2、4、8、12、16、20、24周清洁取肾,采用免疫组织化学染色,定量分析肾脏Ang-2和血栓调节蛋白TM-1表达变化,用逆转录聚合酶链式反应技术（RT-PCR）检测肾脏Ang-2 mRNA的表达。结果：糖尿病组仅于16周和20周时探及肾组织Ang-2 mRNA表达;免疫组化显示糖尿病肾脏12周时皮质区肾小管周围出现Ang-2着染微血管,16周表达最强;整个实验期间对照组未探及Ang-2 mRNA和蛋白表达;TM-1突出表达于肾小球,糖尿病组2~20周肾小球TM-1着染显著高于对照组（P〈0.001）,峰期在4~16周,24周时低于对照组,但无统计学意义（P〉0.05）,TM-1表达变化与肾重/体重、肾小球面积和体积呈正相关。结论：糖尿病肾脏中后期皮质区肾小管管周围存在Ang-2着染的新生微血管,Ang-2和TM-1的异常表达与肾脏新生血管生成有关。

The Study on the Relationship Between the Expression of Angiopoietin 2 and Thrombomodulin-1 and the Renal Angiogenesis of Diabetic Rats

Objective：To explore the relationship between the expressions of angiopoietin - 2（Ang- 2） and thrombormodulin- 1 （TM - 1） and renal angiogenesis of diabetic rats. Methods： Streptozotocin - induced diabetic rats were divided into the diabetic and control groups. The expressions of ang- 1 and TM - 1 in renal tissue of rats were detected by immunohisochemistry at the 2nd,4 th,8 th, 12 th, 16 th, 20 th and 24th weeks, and Ang- 2 mRNA in kidney by RT- PCR at the same time points. The levels of Ang- 1 and TM - 1 were quantified by computer image analysis. Results- In diabetic group, Ang - 2 mRNA in renal tissue was only detected at the 16th and 20th weeks. Ang- 2 - expressing peritubular microvesscl in renal cortex was found by immunohistochernistry from the 12th week to the 24th week with peak level at 16 week, but not detected before the 8th weeks. In the control group, no detectable Ang- 2 mRNA and immunostaining were found in renal tissue. The expression of TM- 1 was mainly found in glomeruli. TM - 1 staining level in diabetic glomeruli increased significantly, compared with that in the control group at the same time points from the 2nd week to 20th week（P〈0.001）with peak levels from the 4th week to the 16th week. It decreased at 24 week but with no significance （P 〉0.05）. TM- 1 level in diabetic renal tissue was correlated direedy with renal/body weight, glomerular volume, and glomerular area respectively. Conclusion： The quantity of the glomerular capillaries in cliabetic renal ecrtex increases apparently in early and middle stages. There is the formation of new peritubular microvessets in diabetic renal cortex in middle and latstages. The unusual changes of Ang- 2 and TM- 1 are connected with angicgensis in diabetic kidney.