他克莫司对糖尿病大鼠肾小管间质转分化的影响  

Effects of tacrolimus on the transdifferentiation of renal tubulointerstitium of diabetic rats

作　　者：夏林[1] 赵莉[1] 苏双全[1] 胡梅芬[1] 吴永贵[1] 

机构地区：[1]安徽医科大学第一附属医院肾脏内科,合肥230022

出　　处：《安徽医科大学学报》2012年第4期392-395,共4页Acta Universitatis Medicinalis Anhui

基　　金：教育部高等学校博士学科点专项科研基金(编号:20093420110003);安徽省教育厅自然科学基金资助课题(编号:2006KJ316B)

摘　　要：目的探讨他克莫司(FK506)对糖尿病大鼠肾小管间质转分化的影响。方法应用链脲佐菌素(65 mg/kg)腹腔注射建立大鼠糖尿病模型。分别给予FK506 0.5、1.0 mg/kg.d灌胃,共4周。随机分对照组、模型组、FK506(0.5,1.0 mg/kg)组。4周后观察大鼠肾重/体重(RKW)与尿白蛋白排泄率(AER),并行肾小管-间质病理形态学分析。应用免疫组化法检测肾组织中E-钙黏蛋白(E-cadherin)、α-平滑肌肌动蛋白(α-SMA)与波形蛋白(Vimentin)的表达。结果FK506 1.0 mg/kg给药组大鼠相对肾重、肾小管-间质损伤指数明显低于模型组(P<0.05,P<0.01),FK506 0.5、1.0 mg/kg给药组大鼠AER水平明显低于模型组(P<0.05,P<0.01)。免疫组化显示模型组肾小管间质E-cadherin表达阳性面积明显低于对照组(P<0.01),FK506 0.5、1.0 mg/kg给药组表达阳性面积明显高于模型组(P<0.01),模型组肾小管α-SMA与Vimentin表达明显高于对照组(P<0.01),FK506 0.5、1.0 mg/kg给药组表达明显低于模型组(P<0.01)。结论 FK506可部分上调E-cadherin及下调α-SMA与Vimentin在肾小管间质中的表达,抑制糖尿病大鼠肾小管-间质转分化,从而起到肾脏保护作用。Objective To investigate the effects of tacrolimus（ FK506） on the transdifferentiation of renal tubu- lointerstitium of diabetic rats. Methods Diabetes was induced with streptozotocin in rats,and FK506（ 0. 5,1. 0 mg/kg） was orally administered once a day for 4 weeks. 24 hour urinary albumin excretion rate（ AER） were meas- ured. Tubulointersititium pathologic injury was observed by light microscopy. E-cadherin and α-smooth muscle actin （ α-SMA） and Vimentin were detected by immunohistochemistry. Results Increased relative kidney weight （ RKW） was significantly reduced by FK506（ 1. 0 mg/kg） treatment （ P 0. 05） . Elevated AER was markedly at- tenuated by FK506（ 0. 5,1. 0 mg/kg） treatment（ P 0. 05,P 0. 01） . Compared with control group,E-cadherin in renal tubular epithelial cells was markedly decreased（ P 0. 01） ,but α-SMA and Vimentin significantly increased in diabetic rats（ P 0. 01） . FK506（ 0. 5 and 1. 0 mg/kg） treatment could reduce the increased expression of α- SMA and Vimentin（ P 0. 01） ,increase the expression of E-cadherin（ P 0. 01） . Conclusion FK506 can up-reg- ulate the expression of E-cadherin and down-regulate the expression of a-SMA and vimentin in diabetic renal tubu- lointerstitium cells and restrain the process of tubulointerstitium cells transdifferentiation in diabetic rats which may playing a role in renal protection.

关 键 词：糖尿病肾病 他克莫司 肾小管-间质 转分化 

分 类 号：R587.24[医药卫生—内分泌] R979.5[医药卫生—内科学]