ACEI对糖尿病大鼠视网膜VEGF表达的作用

Effects of ACEI on retinal VEGF expression in diabetic rat

目的探讨血管紧张素转化酶抑制剂(ACEI)对糖尿病大鼠视网膜血管内皮生长因子(VEGF)表达的影响。方法腹腔注射链脲佐菌素制作大鼠糖尿病模型,与正常大鼠随机分别实施ACEI福新普利、β-受体阻滞剂心得安和安慰剂治疗。24周后,应用酶联免疫吸附法、免疫组织化学法、Western blot技术和实时定量逆转录-多聚酶链反应分别检测血浆、玻璃体和视网膜VEGF mRNA及蛋白表达。结果糖尿病鼠玻璃体视网膜VEGF mRNA及蛋白表达显著高于对照组,ACEI治疗后则显著减少。糖尿病鼠心得安治疗后,玻璃体视网膜VEGF蛋白及基因表达无明显改变,ACEI治疗组玻璃体视网膜VEGF mRNA及蛋白表达明显低于心得安治疗组,两组之间血压的差异无统计学意义。结论ACEI对糖尿病大鼠视网膜组织VEGF表达的影响独立于它的抗高血压作用,ACEI治疗伴或不伴高血压的糖尿病视网膜病变(DR)不依赖其降压作用。

Objective An angiotensin-converting enzyme inhibitor （ACEI） reduce the risk of progression of diabetic retinopathy （DR）. However,the mechanisms underling the effect of ACEI on DR remain largely unidentified. This study was to determine the effects of ACEI on retinal vascular endothelial growth factor （VEGF） expression in diabetic rat. Methods The streptozotocin （60 mg/kg） was intraperitoneally injected to establish the diabetic model in 24 male SD rats as experimental group, and compound citric acid solution was injected in 24 male SD rats as control. The rats from experimental group and control group were divided into ACEI fosenopril sodium-treated group, β-adrenergic blocker propranolol-treated group, or vehicle for 24 weeks group. Enzyme linked immunosorbent assay, immunohistochemistry, Western blot and real-time reverse transcription-polymerase chain reaction were used to assess the expression of VEGF protein and mRNA. Results Vitreous fluid and retinal VEGF protein and retinal VEGF mRNA expression were higher in diabetic rats than in control groups and showed a significant reduction in fosenopril sodium-treated diabetic rats （P 〈 0. 01 ）. There was no significant difference between diabetic rats and propranolol- treated diabetic rats （ P 〉 0.05 ） , but there was a significant difference between propranolol-treated diabetic rats and fosenopril sodium-treated diabetic rats in the expression of VEGF protein and mRNA （P 〈 0. 01 ） without any significant difference in systolic blood pressure in the latter two groups （P 〉 0.05）. Conclusion The effects of ACEI on retinal VEGF expression is independent of its anti-hypertensive action. ACEI could offer particular benefits beyond blood pressure reduction in the treatment of diabetic retinopathy with or without hypertension.