阿霉素肾病模型中肾病蛋白、α-平滑肌肌动蛋白、基质金属蛋白酶-9表达的时相变化  

Expression of nephrin,α-SMA and MMP-9 in different pathological process in Adriamycin-induced nephropathy rat model

作　　者：龚晶[1] 甘卫华[1] 郑君[1] 曾智凤[1] 张爱青[1] 李善文[1] 喻春钊[1] 

机构地区：[1]南京医科大学第二附属医院小儿肾脏科,江苏南京210003

出　　处：《中国医药导报》2013年第36期26-29,33,共5页China Medical Herald

基　　金：国家自然科学基金资助项目(编号81172269)

摘　　要：目的研究阿霉素肾病模型不同时相中肾病蛋白(nephrin)、α-平滑肌肌动蛋白(α-SMA)、基质金属蛋白酶(MMP)-9表达变化。方法采用间隔2周2次尾静脉注射阿霉素的方法复制大鼠阿霉素肾病模型,实验分对照组(正常大鼠28只)和模型组(阿霉素肾病大鼠28只),观察2、4、8、12周各项指标的变化,包括24 h尿蛋白、血浆白蛋白和总胆固醇的检测,采用Western-blot法检测肾皮质部nephrin的蛋白表达,采用荧光定量PCR检测肾组织α-SMA的表达,采用ELISA法检测血清MMP-9的表达。结果阿霉素肾病大鼠模型组蛋白尿持续增加,12周末病理表现为肾小球节段性硬化。Nephrin蛋白的表达2周时已出现减少,8周时明显减少,持续至12周时仍未见恢复,与尿蛋白定量呈负相关。α-SMA mRNA的表达2周时开始增加,呈时间相关性递增,其表达与尿蛋白定量呈正相关。血清中MMP-9的表达2周时出现显著减少,呈时间相关性递减,与24 h尿蛋白定量呈负相关。结论通过间隔2周尾静脉注射阿霉素的方法复制阿霉素肾病动态进展模型,nephrin、α-SMA、MMP-9在各不同时相均参与肾病进展。Objective To dynamically observe the expression of nephrin,α-SMA and MMP-9 in different pathological mechanism in Adriamycin-induced nephropathy rat model. Methods The rat Adriamycin nephrosis model was constructed by injecting Adriamycin 4 mg/kg into tail vein and 3.5 mg/kg two weeks later. 56 rats were devided into normal group and model group with 28 rats in each group. The blood and urinary indicators were detected at 2nd,4th,8th and 12th weeks while the pathological changes of the renal tissues were observed under light microscope. Protein expression of nephrin in cortex of kidney was detected by western blot. The mRNA expression of α-SMA in cortex of kidney was examined by RT-PCR. Serum MMP-9 was tested by ELISA. Results Proteinuria of adriamycin nephrosis rats in model group increased continuesly,pathology was glomerular sclerosis of segmental over the 12 weekend. Nephrin protein expression had been reduced at 2 weeks,8 weeks decreased significantly,while continuing to 12 weeks with no recovery,and it was negatively correlated with urinary protein quantitative. Alpha SMA mRNA expression began to increase in 2 weeks with the time correlation increasing,and its expression and quantitative urine protein were positively correlated. Serum in the expression of MMP9 in 2 weeks,there was a significant decrease,with the time correlation diminishing,and it was negatively correlated with 24 h urine protein quantitative. Conclusion Through the method of interval of 2 weeks tail intravenous injection of Adriamycin replication dynamic progress model of Adriamycin nephrosis nephrin,alpha SMA,MMP9 in each phase are involved in kidney disease progress at the same time.

关 键 词：阿霉素肾病 NEPHRIN Α-SMA MMP-9 

分 类 号：R563.9[医药卫生—呼吸系统]