【摘要】 目的 探讨Tacrolimus（FK506）是否通过足细胞的保护作用减轻糖尿病大鼠尿白蛋白排泄。方法 将40只大鼠按随机数表法分为对照组（C组）、糖尿病（diabetes mellitus,DM）模型组（DM组）、DM+FK506 0.5mg·kg^-1·d^-1给药组（FK506 0.5组）及DM+FK506 1.0 mg·kg^-1·d^-1给药组（FK506 1.0组）,每组10只。采用链脲佐菌素（streptozotocin,STZ）腹腔注射建立糖尿病模型,FK506灌胃给药。4周后大鼠24 h尿白蛋白测定采用酶联免疫方法,电镜下观察肾小球足细胞病理组织学改变,应用免疫荧光与Western blot检测肾组织Nephrin和Podocin表达。结果 DM组大鼠24 h尿白蛋白排泄率（albumin excretion rate,AER）明显高于对照组（P<0.01）,FK506 0.5与1.0mg/kg给药组大鼠AER水平明显低于模型组（P<0.05,P<0.01）。透射电镜观察DM组肾小球基底膜增厚、结构模糊不清,系膜基质增多,足细胞损伤,与DM组比较,FK506 0.5、1.0组肾组织超微结构改变有不同程度改善。免疫荧光显示Nephrin和Podocin在C组大鼠肾小球呈线状均匀分布;DM组大鼠肾小球表达明显减少,且呈颗粒状不均匀分布;FK506 0.5组和FK506 1.0组Nephrin和Podocin表达不同程度增加,呈线状及颗粒状分布。Western blot显示DM组Nephrin和Podocin较C组表达明显下降;FK506 0.5组和FK506 1.0组Nephrin和Podocin量较DM组明显增加（P<0.01）。结论 FK506能减少糖尿病大鼠尿白蛋白排泄,改善肾小球足细胞病变,其机制可能与上调Nephrin和Podocin表达有关。更多还原

【Abstract】 Objective To investigate the protective effect of Tacrolimus（FK506） on the podocytes in rat diabetic model,and evaluates its machanism.Methods According to the random number table method,40 adult male rats were divided into 4 groups:control group（n= 10）,model group（n= 10）,model group treated with FK506 0.5 mg·kg^-1day^-1（n = 10）,and model group treated with FK506 1.0 mg·kg^-1·day^-1（n= 10）.Diabetes was induced with streptozotocin（65 mg/kg,intraperitoneal injection） in rats,and tacrolimus was orally administered once a day for 4 weeks.24-ho urinary albumin excretion rate（AER） was determined by enzyme immunoassay.Kidney pathologic injury was observed by electron microscope.The expression of Nephrin and Podocin was detected by immunofluorescence and Western blot Results Increased AER was markedly attenuated by FK506 treatment with 0.5 and 1.0 mg/kg（P<0.05,or P<0.01）.Under the electron microscope,model group showed a significantly widened glomerular basement membrane,disordered,wide and fused podocyticprocess.The above lesions in groups treatment with FK506 0.5 or 1.0 mg/kg were alleviated as compared with model group（P<0.05）.As compared with control group,the staining of glomeruli in model group was attenuated,more dispersed and clustered,and this diabetes-induced loss of glomerular Nephrin and Podocin expression was largly prevented in FK506-treated diabetic rats.Western blot showed that the expression of Nephrin and Podocin proteins was reduced in the kidney of diabetic rats,and FK506 treatment significantly increased the expression of Nephrin and Podocin proteins（P<0.01）.Conclusions FK506 could ameliorate renal structure and function injury in early experimental diabetic rats,which may be partly correlated with the up-regulated expression of Nephrin and Podocin.更多还原