目的:探讨贝那普利(benazepril,BZ)对糖尿病大鼠视网膜微血管病变的保护作用及机制。方法:链脲佐菌素ip制备糖尿病大鼠模型,分为糖尿病组(DM)、贝那普利治疗组(BZ),同时设立正常对照组(Con)。治疗组每天灌胃给予BZ10mg/kg。24wk后放射免疫法测定血浆AngⅡ水平,免疫组织化学法和Westernblot技术检测视网膜VEGF蛋白表达,透射电镜观察视网膜血管基底膜厚度变化。结果:与Con组相比,DM组大鼠血浆AngⅡ水平明显增高(P<0.01),视网膜VEGF蛋白表达显著增强(P<0.01),视网膜微血管基底膜明显增厚;与DM组相比,BZ治疗后大鼠血浆AngⅡ水平明显降低(P<0.05),视网膜VEGF蛋白表达则显著减弱(P<0.01),视网膜微血管基底膜增厚明显减轻。结论:BZ可通过抑制血浆AngⅡ水平,减少糖尿病大鼠视网膜组织VEGF表达,抑制视网膜微血管基底膜增厚。

AIM:To explore the mechanism of angiotensin converting enzyme inhibitor(ACEI)-benazepril(BZ) on the protection of diabetic retinopathy.METHODS:Streptozotocin(60mg/kg)was intraperitoneally injected to establish the diabetic model in 24 male SD rats as experimental group,model rats were divided into diabetes mellitus(DM) group and benazepril(BZ) group,control group was also established.BZ was given to treatment group at dose of 10mg/kg per day by gavage.24 weeks later,plasma angiotensin Ⅱ was detected and immunohistochemistry,Western blot were used to assess the expression of VEGF protein in retina.The changes of basement membrane thickness(BMT) of retinal vessels were observed by transmission electron microscopeRESULTS:The level of plasma angiotesin Ⅱ and retinal VEGF protein expression were significantly higher in DM rats than in control groups and showed a significant reduction in BZ treated diabetic rats(P<0.01).BMT of retinal vessels increased in DM rats and extenuated in BZ treated diabetic rats.CONCLUSION:BZ can reduce retinal VEGF protein expression by inhibiting the level of plasma angiotensin Ⅱand ameliorate BMT of retinal vessels in DM rats.

中国辽宁省科技攻关计划资助项目(No.2009225010-45);中国辽宁省教育厅科研基金资助项目(No.2008404)