大鼠单侧输尿管梗阻后肾脏Notch1/Jagged1的表达及其意义

Expression and significance of Notch1/Jagged1 in rat kidney with unilateral ureteral obstruction

目的:观察大鼠单侧输尿管梗阻(UUO)后不同时期Notch1/Jagged1、纤维连接蛋白(FN)表达的变化,探讨在肾脏间质纤维化发病机制中的意义。方法:建立大鼠UUO模型,采用半定量逆转录聚合酶链反应(RT-PCR)和westernblotting动态观察(第1、3、7、14天)梗阻侧肾脏及假手术对照组Notch1/Jagged1mRNA、蛋白和FN的表达。结果:UUO模型梗阻侧肾脏Notch1/Jagged1mRNA蛋白及FN蛋白在输尿管结扎后第1、3、7、14天不同时间点均显著高于对照组和非梗阻侧肾脏(P<0.05或P<0.01),Notch1/Jagged1mRNA在第7天达高峰,但Jagged1于第1天达高峰,Notch1、FN在第14天达高峰。结论:在整体条件下,随着肾间质纤维化程度的加重,FN聚积也随之增加,同时Notch1/Jagged1表达增强,提示Notch1/Jagged1信号通路在肾间质纤维化发病机制中起重要作用。

Objective： To investigate the role of Notch1/Jagged1 activation pathway in the development of renal tubulointerstitial fibrosis in vivo. Methods： Rats were sacrificed aftcrl day, 3 days, 7 days and 14 days of uretcral obstruction（UUO）, and sham-operated rats were sacrificed as the control. Notch1/Jaggcd1 mRNA and protein and Fibronectin （FN） were analyzed with semi-quantitative RT-PCR and western blot. Results： Noteh1/Jagged1, FN mRNA and protein levels of the UUO group at the 1st, 3rd, 7th, 14th days in the kidneys of rats with obstructed kidneys, were significantly increased （P 〈 0.05 or P 〈 0.01 ）, compared to sham-operated rats. Notch1/Jagged1 mRNA expression were peaked 7 days after UUO （P 〈 0.05）. Jagged1 protein expression was peaked 1 day after UUO. The levels of Notch1 and FN protein expression were peaked 14 days after UUO （P 〈 0.05）. Conclusion： Expressions of Notch1/Jaggcd1 are increased in renal tissue after UUO. Notch1/Jagged1 signaling pathway may be involved in UUO rats and plays a concordant role in the pathogcnesis of renal interstitial fibrosis.