他克莫司对糖尿病大鼠肾小管间质转分化的影响

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。

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

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.