霉酚酸酯对糖尿病大鼠肾组织Nephrin与Podocin表达的影响及机制  

Effects of mycophenolate mofetil on the expression of Nephrin and Podocin and its mechanism in the kidney of diabetic rats

作　　者：董婧[1] 吴永贵[1] 任克军[1] 齐向明[1] 梁超[1] 张炜[1] 袁亮[1] 方芳[1] 沈际佳[2] 

机构地区：[1]安徽医科大学第一附属医院肾脏内科,安徽合肥230022 [2]安徽医科大学病原生物学教研室,安徽合肥230032

出　　处：《中国药理学通报》2008年第2期254-258,共5页Chinese Pharmacological Bulletin

基　　金：安徽省自然科学基金资助课题(No070413100);安徽省教育厅自然科学基金资助课题(No2006KJ316B)

摘　　要：目的探讨霉酚酸酯(Mycophenolate mofetil,MMF)对糖尿病大鼠肾组织Nephrin与Podocin蛋白表达的影响及机制。方法建立链脲佐菌素诱导的单侧肾切除大鼠糖尿病模型,将模型大鼠随机分成糖尿病组(DM组)与MMF给药组(DM+MMF组,10mg·kg-1.d-1灌胃给药),另设对照组(C组)。8wk末检测血糖、24h尿白蛋白排泄率(AER)变化,通过免疫组化方法检测肾组织ED-1表达,Westernblot方法检测肾组织Nephrin、Podocin、白细胞介素-1(IL-1)与肿瘤坏死因子-α(TNF-α)蛋白表达。结果DM组大鼠尿AER明显高于C组(P<0.01),DM+MMF组大鼠尿AER明显低于DM组(P<0.05)。DM组大鼠肾小球ED-1阳性细胞数明显高于C组(P<0.01),DM+MMF组肾小球巨噬细胞浸润明显低于DM组(P<0.05)。DM组肾组织Nephrin与Podocin表达较C组分别下降80.2%与65.1%,MMF可明显恢复肾组织Nephrin与Podocin表达(P<0.01)。DM组肾组织IL-1与TNF-α表达较C组分别增加2.8倍与3.8倍,MMF可明显降低肾组织IL-1与TNF-α表达(P<0.01)。结论MMF可能通过恢复糖尿病大鼠肾组织Nephrin与Podocin蛋白表达减少尿白蛋白排泄。Aim To investigate the effect of mycophenolate mofetil（ MMF）on the expression of Nephrin and Podocin and its mechanism in the kidney of diabetic rats. Methods Diabetes was induced with streptozotocin after uninephrectomy, and MMF （ 10 mg ·kg^-1·d^-1 was orally administered once a day for 8 wk. Blood glucose and 24 hours urinary albumin excretion rate （AER） were measured. The expression of ED-1, Nephrin, Podocin, interleukin-1 （ IL-1 ） and tumor necrosis factor-α（TNF-α） protein in the kidney were determined by immunohistochemistry or Western blot analysis. Results Elevated AER was markedly attenuated by MMF treatment（P 〈0. 05）. ED-1-positive cells were significantly increased in glomeruli of diabetic rats, which was effectively suppressed by MMF treat-ment （ P 〈 0. 05 ）. Western blot analysis showed that the expression of Nephrin and Podocin protein was reduced in the kidney of diabetic rats, and MMF treatment significantly increased the expression of Nephrin and Podocin protein（ P 〈 0. 01 ）. The expression of IL-1 and TNF-α protein in the kidney was significantly increased in diabetic rats, which was significantly inhibited by MMF treatment （ P 〈 0. 01 ）. Conclusions MMF could decrease AER in diabetic rats, whose mechanism may be at least partly correlated with upregulating the expression of Nephrin and Podocin in the kidney.

关 键 词：糖尿病肾病 霉酚酸酯 NEPHRIN PODOCIN 

分 类 号：R-332[医药卫生] R322.61