霉酚酸酯对阿霉素肾病大鼠肾小球Nephrin和TGF-β_1表达的影响  

Effects of mycophenolate mofetil on the renal Nephrin and transforming growth factor-β_1 of adriamycin nephritic rats

作　　者：王军建[1] 李少宁[1] 林菲[1] 王列[1] 

机构地区：[1]西安市儿童医院急诊科,西安710002

出　　处：《陕西医学杂志》2013年第1期13-17,共5页Shaanxi Medical Journal

摘　　要：目的:探讨霉酚酸酯(MMF)对阿霉素肾病大鼠肾小球Nephrin、转化生长因子-β1(TGF-β1)蛋白表达的影响。方法:将36只SD大鼠随机分为模型组(n=24)和对照组(n=12)。模型组大鼠尾静脉一次注射盐酸阿霉素(ADR)7mg/kg,对照组大鼠尾静脉注射等容积生理盐水,注射ADR 1周后尿蛋白定量>100mg/24h即为建模成功,共有20只大鼠建模成功,随机又分为肾病模型组(n=10)和MMF干预组(n=10)。MMF干预组每天给予MMF 10mg/kg灌胃,每日1次,共8周。对照组和肾病模型组给予等容积生理盐水灌胃。实验结束后检测各组大鼠24h尿蛋白定量,光镜观察肾脏病理学改变,免疫组化技术和Western-Blotting技术检测Nephrin、TGF-β1的表达。结果:肾病模型组及MMF干预组24h尿蛋白定量、肾小球TGF-β1表达均高于对照组(P?0.05),但MMF干预组上述指标均低于肾病模型组(P?0.05);肾病模型组及MMF干预组肾小球Nephrin表达低于对照组(P?0.05),但MMF干预组Nephrin表达高于肾病模型组(P?0.05)。结论:Nephrin及TGF-β1在阿霉素肾病发病机制中起重要作用;MMF能够增加肾小球Nephrin的表达,抑制TGF-β1的表达,减少阿霉素肾病大鼠尿蛋白的排出,减轻及延缓肾小球硬化,发挥保护肾脏的作用。Objective：To explore effects of Mycophenolate mofetil on expression changes of Nephrin and transforming growth factor-131 （TGF-β1） in adriamycin（ADR） -induced-nephropathy rats. Methods： Thirty-six rats of Sprague-Dawley were divided into two groups： the model group （n =24） and the control group （n = 12）. The rats in the model group were injected with a single dose of ADR （ 7 mg/kg ） via tail-vein, while the rats in the control group were injected with a comparable volume of 0.9% saline. The model was successfully established when the 24 h urinary protein excretion exceeded 100 mg after ADR injection I week, Twenty rats were successful and then were randomly assigned to the ADR nephrosis group （n = 10） and the MMF group（n = 10）. The rats in the MMF group were treated with MMF （ 10 mg/ kg/d ） I g,once a day for 8 weeks,whereas the other rats were received a comparable volume of 0.9 % saline. The 24 h urinary protein excretion was measured and the pathological changes of the renal tissues were observed under light microscope, Immunohistochemical and Western Blotting techniques to de tect the expression of Nephrin and TGF-β1. Results： The 24 h urinary protein and the expression of TGF-131 in the ADR nephrosis group were higher than those in the control group and MMF group （P〈0.05）, and the expression of Nephrin in the ADR nephrosis group was lower than those in the control group and MMF group （P〈0.05）. Conclusions： Nephrin and TGF-β1 play an important role in the pathogenesis of ADR nephrosis MMF decreased the urine albumin excretory rate, and prevent the glomemlar sclerosis in rats with ADR nephrosis, which mechanism may be at least partly correlated with enhancing the expression of Nephrin and inhibiting the expression of TGF-β1 in kidney.

关 键 词：肾病 化学诱导 肾病 药物疗法 免疫抑制剂 治疗应用 蛋白 代谢 转化生长因子β 代谢 @阿霉素霉 @Nephrin 

分 类 号：R692.6[医药卫生—泌尿科学]