敲除背根神经节Fcgr1减弱类风湿关节炎模型大鼠NF-κB/NLRP3通路活化

基础医学与临床 ›› 2021, Vol. 41 ›› Issue (7): 963-969.

敲除背根神经节Fcgr1减弱类风湿关节炎模型大鼠NF-κB/NLRP3通路活化

刘帆, 苏思, 王涛, 袁勃, 马超^*

中国医学科学院基础医学研究所北京协和医学院基础学院人体解剖与组织胚胎学系,北京 100005

收稿日期:2021-03-05 修回日期:2021-05-19 出版日期:2021-07-05 发布日期:2021-06-17
通讯作者: *machao@ibms.cams.cn
基金资助:
国家自然科学基金(81771205,91632113,81801114);中国博士后科学基金(2018M631389);中国医学科学院创新工程(2017-I2M-3-008)

Knocking out Fcgr1 of dorsal root ganglion attenuates the activation of NF-κB/NLRP3 pathway in a rat model of rheumatoid arthritis

LIU Fan, SU Si, WANG Tao, YUAN Bo, MA Chao^*

Department of Human Anatomy, Histology and Embryology, Institute of Basic Medical Sciences CAMS, School of Basic Medicine PUMC, Beijing 100005, China

Received:2021-03-05 Revised:2021-05-19 Online:2021-07-05 Published:2021-06-17
Contact: *machao@ibms.cams.cn

摘要/Abstract

摘要： 目的探讨外周神经元FcγRⅠ调控类风湿关节炎疼痛的机制。方法利用野生型SD大鼠和条件敲除Fcgr1大鼠建立类风湿关节炎模型。设野生型大鼠对照组(control组)、野生型大鼠类风湿关节炎(RA)组和条件敲除Fcgr1大鼠类风湿关节炎(CKO+RA)组,每组7只。用痛觉行为学检测各组大鼠建模前第3、1 d,建模后第3、5、7、9 d机械痛阈值和热痛阈值变化,用荧光原位杂交实验检测条件敲除Fcgr1大鼠背根神经节(DRG)中是否表达Fcgr1 mRNA,用免疫荧光实验检测大鼠DRG中pNF-κB (p65)、NLRP3、IL-1β和IL-18表达和脊髓背角(SDH)胶质细胞活化。结果与control组比较,RA组和(CKO+RA)组大鼠机械和热疼痛阈值均降低,(CKO+RA)组大鼠机械和热疼痛阈值比RA组大鼠明显提高(P＜0.05);与RA组大鼠相比,(CKO+RA)组大鼠DRG中pNF-κB (p65)、NLRP3、IL-1β和IL-18表达明显下调(P＜0.05);SDH中GFAP和Iba1表达降低(P＜0.05)。结论 DRG神经元FcγRⅠ可能通过NF-κB/NLRP3通路促进神经元炎性细胞因子IL-1β和IL-18合成释放,引起SDH胶质细胞活化,参与类风湿关节炎疼痛。

关键词: 类风湿关节炎, 疼痛, 中枢敏化, Fc-gamma receptor Ⅰ(FcγRⅠ), 免疫复合物

Abstract: Objective To explore the mechanism of peripheral neurons FcγRⅠ regulating pain caused by rheumatoid arthritis. Methods Rheumatoid arthritis models were established in 14 wild-type SD rats and 7 Fcgr1 conditional knockout rats. Wild-type rat control group (control group), rheumatoid arthritis group of wild-type rat (RA group) and rheumatoid arthritis group of Fcgr1 conditional knockout rat (RA+CKO group) were established. Pain behavior was used to detect the changes of mechanical pain threshold and thermal pain threshold 3 and 1 days before modeling and 3, 5, 7 and 9 days after modeling. The expression of Fcgr1 mRNA in dorsal root ganglion (DRG) of Fcgr1 conditional knockout rat was detected by fluorescence in situ hybridization. Immunofluorescence staining was used to detect the changes of IL-1β and IL-18 expression in the DRG and activation of glial cells in the spinal dorsal horn (SDH). Results Compared with the control group, the threshold of mechanical and thermal pain in RA group and (RA+CKO) group were decreased (P＜0.05), the mechanical and thermal pain thresholds of the (RA+CKO) group were significantly higher than of RA group(P＜0.05). Compared with the RA group, the expression of pNF-κB, NLRP3, IL-1β and IL-18 and the protein level of GFAP and Iba1 in the SDH of (RA+CKO) rats were significantly decreased (P＜0.05). Conclusions FcγRⅠ of DRG neurons may promote the synthesis and release of inflammatory cytokines IL-1β and IL-18 through NF-κB/NLRP3 pathway, and cause glial cells activation in the SDH, which may play a role in the mechanism causing pain of rheumatoid arthritis.

Key words: rheumatoid arthritis, pain, central sensitization, Fc-gamma receptor I (FcγRⅠ), immune complex

中图分类号:

R322.8

刘帆, 苏思, 王涛, 袁勃, 马超. 敲除背根神经节Fcgr1减弱类风湿关节炎模型大鼠NF-κB/NLRP3通路活化[J]. 基础医学与临床, 2021, 41(7): 963-969.

LIU Fan, SU Si, WANG Tao, YUAN Bo, MA Chao. Knocking out Fcgr1 of dorsal root ganglion attenuates the activation of NF-κB/NLRP3 pathway in a rat model of rheumatoid arthritis[J]. Basic & Clinical Medicine, 2021, 41(7): 963-969.

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