Foxp3磷酸化通过调控调节性T细胞功能对类风湿关节炎大鼠TNF-α抑制状态影响的分子机制  

Molecular mechanism of Foxp3 phosphorylation on the inhibition of TNF-α in rheumatoid arthritis rats by regulating regulatory T cell function

作　　者：李涛[1] 王礼 张廷[3] LI Tao;WANG Li;ZHANG Ting(Department of Bone,The Second Hospital of Yulin,Yulin Shaanxi 719000,China;Department of Surgery,Affiliated Hanjiang Hospital of Xi'an Medical University,Hanzhong Shaanxi 723000,China;Department of Orthopaedics,The Second Affiliated Hospital of Xi'an Jiaotong University,Xi'an Shaanxi 710000,China)

机构地区：[1]榆林市第二医院骨科,陕西榆林719000 [2]西安医学院附属汉江医院外科,陕西汉中723000 [3]西安交通大学第二附属医院骨科,陕西西安710000

出　　处：《临床和实验医学杂志》2020年第9期921-924,共4页Journal of Clinical and Experimental Medicine

基　　金：陕西省卫生厅科研基金项目(编号:2014jm32549)。

摘　　要：目的探究Foxp3磷酸化通过调节性T细胞功能改善类风湿关节炎大鼠肿瘤坏死因子-α(TNF-α)抑制状态的分子机制。方法建立类风湿关节炎大鼠模型,分组为正常组(无特殊处理)、模型组(类风湿关节炎模型)和实验组(类风湿关节炎模型+尾静脉注射TNF-α阻滞剂进行治疗)。酶联免疫吸附(ELISA)检测炎症因子白介素10(IL-10)、白介素17(IL-17)和转化生长因子-β(TGF-β)水平;流式细胞术检测T细胞阳性率;Western Blot检测TNF-α表达以及试剂盒检测Foxp3磷酸酶活性。结果与正常组相比,模型组IL-10、TGF-β水平显著降低,IL-17水平显著升高(P<0.05);与模型组相比,实验组IL-10、TGF-β的水平显著升高,IL-17的水平显著降低(P<0.05)。与正常组相比,模型组CD4^+CD25^+T细胞和CD4^+CD25^+Foxp3^+T细胞检测阳性率均显著降低(P<0.05);与模型组相比,实验组以上指标检测比率均显著增加(P<0.05);与正常组相比,模型组的TNF-α蛋白相对表达量显著增加(P<0.05);与模型组相比,实验组TNF-α蛋白的相对表达量显著降低(P<0.05)。与正常组相比,模型组的Foxp3磷酸酶活性显著降低(P<0.05);与模型组相比,实验组Foxp3磷酸酶活性显著升高(P<0.05)。结论通过尾静脉注射TNF-α阻滞剂治疗后,大鼠炎症反应水平、TNF-α蛋白表达及FOXP^3磷酸酶活性均降低,机制可能是Foxp3磷酸化通过调控调节性T细胞数量及炎症因子的变化参与对类风湿关节炎大鼠抑制状态,从而一定程度缓解类风湿关节炎不良症状。Objective To investigate the molecular mechanism of Foxp3 phosphorylation in the inhibition of TNF-αin rheumatoid arthritis rats through regulatory T cell function.Methods Rat models of rheumatoid arthritis were established and divided into normal group,model group and experimental group(treated by tail vein injection of TNF-αblocker).The levels of inflammatory factors IL-10,IL-17 and TGF-βwere detected by ELISA,the positive rate of T cells was detected by flow cytometry,the expression of TNF-αwas detected by Western Blot and the activity of Foxp3 phosphatase was detected by kit.Results Compared with the normal group,IL-10 and TGF-βlevels in the model group were significantly decreased,and IL-17 levels were significantly increased(P<0.05);Compared with the model group,the levels of IL-10and TGF-βin the experimental group were significantly increased,and the level of IL-17 was significantly decreased(P<0.05).Compared with the normal group,the positive rates of CD4^+CD25^+T cells and CD4^+CD25^+Foxp3^+T cells in the model group were significantly lower(P<0.05).Compared with the model group,the detection ratios of the above indicators in the experimental group were significantly increased(P<0.05).Compared with the normal group,the relative expression of TNF-αprotein in the model group increased significantly(P<0.05).Compared with the model group,the relative expression of TNF-αprotein in the experimental group was significantly decreased(P<0.05).Compared with the normal group,the Foxp3 phosphatase activity of the model group was significantly decreased(P<0.05).Compared with the model group,the Foxp3 phosphatase activity of the experimental group was significantly increased(P<0.05).Conclusion After treatment with TNF-αblocker via tail vein injection,the inflammatory response level,TNF-αprotein expression and FOXP3 phosphatase activity of rats were all reduced.The mechanism may be that Foxp3 phosphorylation regulates the number of regulatory T cells and inflammatory factors Changes involved in the inhibition

关 键 词：大鼠 类风湿关节炎 Foxp3磷酸化 调节性T细胞 TNF-α 

分 类 号：R593.22[医药卫生—内科学]