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

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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 investigate the role of JAK / STAT1 signal transduction pathway in lupus nephritis in MRL / lpr mice and the effect of rapamycin on the activation of JAK / STAT1 signal transduction pathway. Methods MRL / lpr transgenic mice were treated with rapamycin. Immunohistochemistry was used to investigate the distribution of phosphorylated STAT1 in the kidney. Western blot was used to investigate the expression of phosphorylated STAT1 protein. Fluorescent SYBR green fluorescence The real-time quantitative PCR was used to investigate the expression of SOCS-1 mRNA in order to study the activation of STAT1. Results The phosphorylated STAT1 protein in the kidney of MRL / lpr mice was significantly activated and the expression of SOCS-1 gene was increased. The expression of phosphorylated STAT1 protein was decreased and the expression of SOCS-1 gene was decreased in the kidney after rapamycin treatment. Conclusion The activation of JAK / STAT1 signal transduction pathway is associated with the pathogenesis of lupus nephritis. Rapamycin can reduce the expression of JAK / STAT1 signal transduction pathway, which may be one of the mechanisms of rapamycin in the treatment of systemic lupus erythematosus.
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