MRL／lpr小鼠肾组织JAK／STAT信号转导途径的表达和雷帕霉素对其表达的影响  

Expression of JAK/STAT signal transduction pathway and the effects of rapamycin in lupus nephritis-prone MRL/lpr mice

作　　者：董静[1] 蒋艳霞[2] 刘爱国[3] 王少春[3] 杨清锐[1] 张源潮[1] 

机构地区：[1]山东大学山东省立医院风湿免疫科,济南250021 [2]青岛大学医学院附属医院病理科 [3]青岛大学医学院附属医院急诊内科

出　　处：《中华微生物学和免疫学杂志》2007年第6期490-494,共5页Chinese Journal of Microbiology and Immunology

基　　金：山东省教育厅基金(J99K51)

摘　　要：目的探讨JAK/STAT1信号转导途径在MRL/lpr小鼠狼疮肾炎中所起的作用以及雷帕霉素对JAK/STAT1信号转导途径活化的影响。方法采用MRL/lpr转基因鼠,给予雷帕霉素干预治疗后,采用免疫组化方法研究肾脏磷酸化STAT1的组织分布情况,采用Western blot方法研究磷酸化STAT1蛋白的表达,采用SYBR green嵌合荧光法real-time定量PCR研究SOCS-1 mRNA的表达,从而研究STAT1的活化水平。结果MRL/lpr狼疮鼠肾脏的磷酸化STAT1蛋白明显活化,SOCS-1基因的表达升高,给予雷帕霉素治疗后肾脏的磷酸化STAT1蛋白表达降低,SOCS-1基因的表达降低。结论JAK/STAT1信号转导途径的活化与狼疮肾炎的发病相关,雷帕霉素可以降低JAK/STAT1信号转导途径的表达,这可能是雷帕霉素治疗系统性红斑狼疮的机理之一。Objective To explore the role of JAK/STAT1 signal transduction pathway in lupus nephritisprone MRL/lpr mice, and to study the effects of raparoycin on the activation of this pathway. Methods MRL/lpr mice with lupus nephritis were treated with mpamycin. STAT1 expression in kidney was detected by immunohistochemistry and Western blot. Gene expression of the STAT-induced feedback inhibitors suppressor of cytokine signaling 1（SOCS-1 ）, which indicates the activation of JAK/STAT1 signal transduction pathway, was investigated by SYBR green real-time quantitative polymerase chain reaction（PCR）. Results The phosphorylated STAT1 protein was markedly activated in kidney of MRL/lpr mice, the expression of SOCS-1 mRNA was increased. Rapamycin reduced renal phesphorylated STAT1 protein and lowered the SOCS-1 gene expression. Conclusion JAK/STAT1 signal transduction pathway was associated with lupus nephritis. Rapamycin could inhibit the expression of JAK/ STAT1, which implicates one of the mechanisms by which mpamycin treat systemic lupus erythematosus.

关 键 词：雷帕霉素 信号转导和转录活化因子 小鼠 MRL/lpr 狼疮肾炎 

分 类 号：R692[医药卫生—泌尿科学] R96[医药卫生—外科学]