西拉普利对糖尿病大鼠肾小球VEGF、ICAM-1表达的影响

Effects of Cilazapril on the Expression of Vascular Endothelial Growth Factor and Intercellular Adhesion Molecule-1 in Diabetic Rat Glomeruli

目的 探讨血管紧张素转化酶抑制剂西拉普利对糖尿病肾病 (DN)保护作用和对肾小球血管内皮生长因子 (VEGF)和细胞间粘附分子 1(ICAM- 1)表达的影响。方法 采用链脲佐菌素 (STZ)诱发糖尿病 (DM)大鼠模型并给予西拉普利 1mg/ (kg· d)治疗 2周、8周 ,观察大鼠肾小球肥大、肾功能和尿蛋白的变化以及用免疫组织化学及计算机图像分析技术定位、半定量检测 VEGF和 ICAM- 1的表达。结果 2周时糖尿病组肾重 /体重、CCr和 2 4 h尿蛋白升高 ,与对照组比较有显著性差异 (P<0 .0 5 ,P<0 .0 1)。免疫组化提示 ,肾小球 VEGF、ICAM- 1表达也增加 ,8周时达高峰 ,与对照组比较亦有显著性差异 (P<0 .0 1)。西拉普利作用 8周后 ,可降低肾重 /体重、CCr和 2 4 h尿蛋白 ,减少肾小球 VEGF、ICAM- 1表达水平 ,与糖尿病组比较 ,P<0 .0 5。结论 西拉普利可抑制糖尿病大鼠 VEGF和 ICAM- 1的表达 ,延缓糖尿病肾病的发生。

Objective To assess the effect of cilazapril, an angiotensin converting enzyme inhibitor (ACEI), on the protection against diabetic nephropathy and on the expression of vascular endothelial growth factor (VEGF) and intercellular adhesion molecule 1 (ICAM 1) in diabetic rat glomeruli. Methods The rat model of diabetes mellitus (DM) was produced by injection of streptozocin (STZ). After the treatment with cilazapril〔1mg/(kg·d)〕 for 2 weeks and 8 weeks, glomerular hypertrophy, renal function and 24 h urinary protein count were measured, and the expression of VEGF and ICAM 1 were investigated by immunohistochemical technique and Mias 2000 pathology computer image analyzer in diabetic rat glomeruli. Results At 2 weeks, kidney weight/body weight(KW/BW), creatinin clearance rate (CCr) and 24 hours urine protein count increased significantly in DM model group, compared with control ( P<0.05, P <0.01). Meanwhile, by immunohistochemistry, increased levels of glomerular VEGF and ICAM 1 were shown and their peaks were seen at 8 weeks ( P <0.01). Cilazapril could reduce KW/BW, CCr and 24 hours urine protein count and significantly suppress the overexpression of VEGF and ICAM 1 in cilazapril treatment group after 8 weeks, compared with the DM model group( P <0.05). Conclusion Cilazapril can suppress the overproduction of two cytokines,VEGF and ICAM 1, thus preventing the progression of diabetic nephropathy.