阿霉素肾病大鼠模型动态变化及其足细胞数量和nephrin的表达变化  

Dynamic Changes of Adriamycin-induced Nephropathy Rats Model and Change of Podocyte Number and Nephrin Expression in Model

作　　者：杨维娜[1] 于琳华[2] 钱亦华[1] 靳辉[1] 郑黎明[3] 柴云[3] 

机构地区：[1]西安交通大学医学院人体解剖学与组织胚胎学系,陕西西安710061 [2]西安交通大学医学院病理学系,陕西西安710061 [3]西安交通大学医学院形态中心,陕西西安710061

出　　处：《中山大学学报（医学科学版）》2009年第5期512-516,F0002,共6页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：陕西省自然科学基金基础研究计划项目(2000SM48)

摘　　要：【目的】探讨足细胞数量及nephrin在阿霉素肾病大鼠肾小球中的表达变化及意义。【方法】SD大鼠64只分为两组,模型组40只和对照组24只。模型组大鼠间隔2周两次尾静脉注射盐酸阿霉素,对照组大鼠相同时间尾静脉注射等容积生理盐水,各组分别于注射后1周、4周、8周、12周检测血、尿的生化指标,光镜、电镜观察肾脏病理学改变,免疫组化技术观察足细胞数量及nephrin的表达变化。【结果】①根据肾脏病理变化模型可分为两期:急性期(1～4周)和慢性期(5～12周)。光镜检查4周末可见肾小球足细胞肿胀,8周末出现球囊粘连,12周末部分肾小球节段性轻、中度硬化。②1周末足细胞nephrin表达减弱(P<0.05),8周末足细胞数量减少(约是对照组的84%,P<0.05)。③nephrin、足细胞数量与24h尿蛋白定量、尿素氮、血肌酐呈负相关关系;足细胞数量与nephrin呈正相关关系。【结论】①经改良间隔2周两次尾静脉注射阿霉素0.004mg/g,可成功建立急性和慢性阿霉素肾病模型,急性模型病理学改变类似人的微小病变性肾病,慢性模型病理学改变类似人的局灶节段性肾小球硬化(FSGS)。②足细胞nephrin的表达减少和分布方式改变可能是大量蛋白尿发生的重要因素。③FSGS发生时足细胞数量减少了约16%。【Objective】 To investigate the expression and significance of the podocyte number and nephrin in adriamycininduced nephropathy rats. 【Methods】 Sixty-four Sprague-Dawley rats were divided into two groups： the model group （n = 40） and the control group （n = 24）. The rats in the model group were injected with adriamycin via tail-vein twice every two weeks, while the rats in the control group were injected with saline in equal amounts at the same time. The blood and urinary biochemical indicators were detected at week 1, 4, 8, and 12 while the pathological changes of the renal tissues were observed under light microscope and electron microscope. The expression levels of nephrin and the podocyte number were examined by immunohistochemistry. 【Results】 ①Based on the pathological change of the renal tissues, the model was divided into two stage： the acute stage （week 1-4 ） and the chronic stage （week 5-12）. In the end of the fourth week, swollen podocytes were observed. In the end of the eighth week, adhesion between glomeruli and Bowman＇s capsule were observed. In the end of the twelfth week, some mild or midrange glomeruli sclerosis were observed; ②Nephrin presented a weak signal in the end of the first week （P〈0.05） and the podocyte number started to decrease （was about 84 % compared with control group） at the end of the eighth week （P〈0.05）; ③Expression of nephrin and podocyte number were negatively correlated with the 24 h urinary protein, blood urea nitrogen and serum creatinine. Podocyte number was positively correlated with nephrin. 【Conclusions】 ①The acute and chronic adriamycin nephrosis model was successfully established by injecting adriamycin 0.004 mg / g into tail-vein twice every two weeks. The acute model is similar to human minimal change disease and the chronic model is similar to human focal segmental glomerulosclerosis （FSGS）; ② The decrease of nephrin expression and the change of its distribution modality might be the significant fac

关 键 词：阿霉素肾病 足细胞 蛋白尿 NEPHRIN 

分 类 号：R365.69[医药卫生—病理学] R181.2[医药卫生—基础医学]