辛伐他汀对糖尿病大鼠视网膜血管内皮钙黏蛋白表达的影响  

Effect of sinvastatin on VE-cadherin in retinas of rat with diabetes

作　　者：萧鸿[1] 王志云[2] 庞东渤[3] 刘学政[2] 

机构地区：[1]辽宁医学院附属第一医院教务科,锦州121001 [2]辽宁医学院解剖学教研室,锦州12100 [3]辽宁医学院附属第一医院眼科,锦州121001

出　　处：《眼科研究》2010年第4期325-329,共5页Chinese Ophthalmic Research

基　　金：辽宁省科学技术计划项目资助(2003225007)

摘　　要：目的观察链脲佐菌素(STZ)诱导的糖尿病视网膜血管内皮钙黏蛋白(VE-cadherin)的表达及辛伐他汀对VE-cadherin表达的影响,探讨他汀类药物可能的非调脂性治疗作用。方法尾静脉注射STZ法建立糖尿病大鼠模型,造模成功48只。成模次日起,24只大鼠每日给予辛伐他汀20 mg/kg灌胃为辛伐他汀组,24只等量生理盐水灌胃为糖尿病组;另选24只大鼠作为正常对照组。分别在造模后2、5、8周各组取8只大鼠采用伊凡思蓝(EB)法检测视网膜的渗透性,免疫组织化学和Western blot法检测各组大鼠视网膜VE-cadherin的表达情况。结果与正常对照组比较,辛伐他汀组和糖尿病组大鼠体重明显下降,差异均有统计学意义(P<0.01),血糖显著上升,差异均有统计学意义(P<0.01)。与糖尿病组大鼠比较,各时间点辛伐他汀组大鼠体重均明显上升,而血糖均显著下降(P<0.05)。免疫组织化学分析证实,VE-cadherin在糖尿病组大鼠视网膜血管呈黄褐色阳性表达。Western blot分析表明随着糖尿病视网膜病变(DR)的发生发展,糖尿病组视网膜血管表达VE-cadherin的量显著减少,与正常对照组和辛伐他汀组比较,差异均有统计学意义(P<0.05)。糖尿病组和辛伐他汀组EB渗透量明显高于正常对照组(P<0.01),辛伐他汀组低于糖尿病组(P<0.05)。结论STZ诱导的糖尿病大鼠视网膜血管中VE-cadherin表达量减少,辛伐他汀可改善这种改变,提示辛伐他汀对DR有预防和治疗作用。Background The primary mechanism of diabetic retinopathy is the change of permeability of retinal blood capillary.Adhesion connection is the predominant mode of intercellular connection among retinal capillary endothelial cells,and vascular endothelium-cadherin mediates the adhesion of vascular endothelial cells to maintain the stability of intercellular connection and cell gap.ObjectiveThe aim of the present study is to investigate the expression of VE-cadherin in the retina of streptozotocin（STZ）-induced diabetes mellitus（DM） rat and assess the effect of simvastatin on the expression of VE-cadherin and the non-lipid therapy of simvastatin in the pathogenesis of diabetic retinopathy.MethodsDiabetic models were established in 48 SD rats by the intraperitoneal injection of streptozotocin（STZ）.Simvastatin（20mg/kg·d） was administered by gavage from the second day in 24 rats and the equivalent amount of normal saline solution was used at the same way in other 24 model rats.Twenty-four normal SD rats were as control group.The animals were sacrificed in 2,5,8 weeks after injection of STZ and the retina was isolated.Vascular permeability was quantified by analyzing albumin leakage using Evans blue method.VE-cadherin expression in retina was detected using immunohistochemistry and Western blot analysis.ResultsThe body weight was significantly declined and blood glucose level was considerably increased in DM group and simvastatin group compared with control group（P0.01,P0.01）,and the body weight was significantly higher but the blood glucose level was lower in simvastatin group than the DM group（P0.05） in various time points.Immunohistochemistry revealed that the expression of VE-cadherin was detected and localized on retinal vessels of diabetic rats,and the expression level of VE-cadherin was significantly decreased in STZ-induced diabetic rat retinas with the progression of diabetes.And the expression level of VE-cadherin in DM group showed a significant difference compared with control and simv

关 键 词：血管内皮钙黏蛋白 糖尿病视网膜病变 辛伐他汀 

分 类 号：R774.1[医药卫生—眼科] R988.1[医药卫生—临床医学]