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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-1mR-NA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。
Objective: To investigate the expression changes of angiopoietin-1 (Ang-1) and thrombomodulin-1 (TM-1) in the kidney of diabetic rats and its relationship with renal microangiopathy. Methods: Nephropathy model of STZ-induced diabetic rats was established. Normal control group and model group were given 2, 4, 8, 12, 16, 20, 24 weeks. The expression of Ang-1 and TM- The expression of Ang-1mR-NA in kidney was observed by RT-PCR and the correlation was analyzed. Results: At 4 and 8 weeks, the expression of Ang-1 mRNA in kidney increased significantly in diabetic group and significantly lower than that in control group at 24 weeks. Immunohistochemical staining of glomerular Ang-1 in diabetic group at 4-24 weeks was significantly higher than that in control group , Peaked at 4-8 weeks and gradually decreased 12 weeks later. Glomerular TM-1 in diabetic group was significantly increased from 2 to 20 weeks, and there was a positive correlation between Ang-1 and TM-1. CONCLUSIONS: Abnormal changes of Ang-1 and TM-1 in diabetic nephropathy are observed in early stage, early stage and down-regulated expression, and this change may be related to the generation of neovascularization in diabetic nephropathy.