JAK/STAT1信号转导途径在MRL/lpr狼疮鼠不同器官中的活化研究

Activation of JAK/STAT1 signal transduction pathway in different organs of MRL/lpr lupus mice

目的探讨Janus蛋白酪氨酸激酶(JAK)/信号转导和转录激活子1(STAT1)信号转导途径在MRL/lpr狼疮鼠肾脏、肺脏、脑等不同器官中的活化和作用。方法实验组是12周龄以上已经发病的MRL/lpr雌性小鼠．对照组是未发病的同龄MRL/lpr雌性小鼠。采用免疫组织化学方法研究肾脏中磷酸化STAT1的组织分布情况。采用Western blot方法研究STAT1磷酸化蛋白表达,采用SYBR greenⅠre- M-time定量聚合酶链反应(PCR)研究SOCS-1 mRNA的表达；并与肺脏、脑相对比。结果MRL/lpr狼疮鼠STAT1磷酸化蛋白在各器官均明显活化。肾脏和肺脏的STAT1磷酸化蛋白活化较脑组织明显；肾脏、肺脏和脑组织的SOCS-1基因的表达均升高．但肾脏的SOCS-1基因表达升高程度低于肺脏和脑组织。结论JAK/STAT1信号转导途径的异常可能参与和促进了系统性红斑狼疮(SLE)各器官病理损害的发生；狼疮肾炎的病理损害还可能与SOCS-1的负反馈调节作用降低有关。

Objective To explore the activation and function of Janus protein-tyrosine kinase （JAK）/ signal transducer and activator of transcription （STATI） signal transduction pathway in kidney, lung and brain of MRL/lpr mice. Methods MRL/lpr mice with systemic lupus erythematosus （SLE） were studied at the age of 12 weeks up. Non-SLE MRL/lpr mice were used as controls. We used phosphospecific antibodies to detect STATI activation in kidney, lung and brain by immunohistochemistry and Western blots. Gene expression of the STAT induced feedback inhibitors of cytokine signaling 1 （SOCS- 1 ） was investigated by SYBR green I real-time reverse transcriptase polymerase chain reaction （PCR）. Results Phosphorylation of STATI protein was markedly activated in these three organs, although renal and pulmonary STATI activation were much more evidently activated. SOCS-I gerte expression increased in all three organs, while renal SOCS-I gene expression increased less than lung and brain. Conclusion The activation of JAK/STATI signal transduetion pathway may be pathogenic in the organ involvement and progression of SLE. The pathogenesis of lupus nephritis may also be associated with the down-regulation of SOCS-I feedback inhibition.