CD40/肿瘤坏死因子受体相关因子1和NF-κB依赖性促炎基因在类风湿性关节炎患者中的表达  

CD40/TNF receptor associated factor 1 expression and NF-κB-dependent proinflammatory gene expression in rheumatoid arthritis

作　　者：程韬[1] 武剑[1] 周玲[2] 何觅春[1] 徐耀增[3] 王鸣军[1] Cheng Tao;Wu Jian;Zhou Ling;He Michun;Xu Yaozeng;Wang Mingjun(Department of Rheumatology and Immunology,the First Affiliated Hospital of Soochow University,Suzhou 215000,China;Department of Nephrology,the First Affiliated Hospital of Soochow University,Suzhou 215000,China;Department of orthopedics,the First Affiliated Hospital of Soochow University,Suzhou 215000,China)

机构地区：[1]苏州大学附属第一医院风湿免疫科,苏州215000 [2]苏州大学附属第一医院肾内科,苏州215000 [3]苏州大学附属第一医院骨科,苏州215000

出　　处：《中华医学杂志》2019年第35期2745-2749,共5页National Medical Journal of China

基　　金：国家自然科学基金(81600565,81601415);江苏省卫生计生委面上科研课题(H201617).

摘　　要：目的探讨CD40/肿瘤坏死因子受体相关因子1(TRAF1)信号通路在类风湿性关节炎(RA)患者中的分子机制。方法收集16例2015至2017年在苏州大学附属第一医院骨科接受膝关节或髋关节置换术的活动性RA患者和9例骨折患者(对照组)。所有患者均获得滑膜组织和血清。用酶联免疫吸附实验、免疫组化法检测CD40、TRAF1及NF-κBp65在血清和组织中的表达。用实时定量聚合酶联反应(RT-PCR)检测NF-κB相关基因的表达,包括细胞因子、趋化因子(MCP-1)和黏附分子(ICAM-1、VCAM-1)。结果RA患者滑膜组织CD40和TRAF1阳性面积(%)分别为28.7±5.4及34.3±4.8,与对照组(分别为21.2±9.5及21.6±8.7)相比差异有统计学意义(P<0.05)。RA患者滑膜组织中总NF-κB p65、磷酸化NF-κB p65蛋白的表达以及与NF-κB相关的细胞因子、趋化因子、黏附分子(ICAM-1)表达明显高于对照组。结论CD40/TRAF1可能作为NF-κB活化和NF-κB依赖性促炎基因的正性调节通路在RA中起重要作用。Objective To investigatea cellular/molecular mechanism of the CD40/TRAF1 signalling pathway involved in Rheumatoid arthritis(RA).Methods 16 patients with active RA and 9 patients with Fractures who underwent total knee or hip replacement in The First Affiliated Hospital of Soochow University were included in the study.Synovial tissues(ST)and serum were obtained from each patient.The CD40,TRAF1,NF-κB p65 were detected by ELISA and Immunohistochemistry in serum and tissue respectively.Real time-PCR(RT-PCR)was applied to measure NF-κB-related gene expression.Results CD40 and TRAF1 positive area(%)in RA patients were 28.7±5.4,34.3±4.8 respectively,which were significantly higher(P<0.05)than Fracture controls(21.2±9.5,21.6±8.7 respectively).The expression of total NF-κB p65,and phospho-NF-κB p65 proteins,as well as NF-κB-related gene expression,including cytokines(TNFα,IL-6),chemokines(MCP-1),and adhesion molecules(ICAM-1)were significantly higher in the ST of RA patients compared to Fracture controls.Conclusion It is thus possible that the CD40/TRAF1 pathway acted as a positive regulator through NF-κB activation and NF-κB-dependent proinflammatory genes in RA.

关 键 词：CD40 肿瘤坏死因子受体相关因子1 NF-ΚB 类风湿关节炎 

分 类 号：R593.22[医药卫生—内科学]