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中国循证儿科杂志

中国循证儿科杂志 ›› 2023, Vol. 18 ›› Issue (6): 456-459.DOI: 10.3969/j.issn.1673-5501.2023.06.009

• 论著 • 上一篇    下一篇

NLRP3炎症小体及相关炎症介质在全身型幼年特发性 关节炎中治疗前后的水平变化

李艳蝶,卢美萍   

  1. 浙江大学医学院附属儿童医院风湿免疫过敏科 国家儿童健康与疾病临床医学研究中心 杭州，310052
  • 收稿日期:2023-02-16 修回日期:2023-12-25 出版日期:2023-12-25 发布日期:2024-01-22
  • 通讯作者: 卢美萍

Changes in the level of NLRP3 inflammasome before and after treatment in systemic juvenile idiopathic arthritis

LI Yandie, LU Meiping   

  1. Department of Rheumatology Immunology＆Allergy, Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou 310052, China
  • Received:2023-02-16 Revised:2023-12-25 Online:2023-12-25 Published:2024-01-22
  • Contact: LU Meiping

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摘要： 背景：针对IL-1或IL-6单克隆抗体开发的新型生物制剂药物对部分全身型幼年特发性关节炎(SJIA)患儿的疗效不佳。亟待通过进一步对发病机制的研究来探索新的治疗策略。 目的：探讨核苷酸结合寡聚化结构域样受体蛋白3（NLRP3炎症小体）及相关炎症介质在SJIA发病机制中的作用。 设计：病例对照研究。 方法：纳入活动期SJIA患儿，以同期在医院体检的健康儿童为对照。取SJIA患儿激素治疗前和治疗2周、8周时的外周静脉血标本，健康儿童采集体检时的外周静脉血标本，提取外周血单个核细胞（PBMCs）。分别通过qRT-PCR、酶联免疫吸附试验（ELISA）和Western免疫印迹法检测NLRP3及相关炎症介质的mRNA和蛋白表达水平。 主要结局指标：NLRP3及相关炎症介质的表达水平。 结果：病例组纳入33例SJIA患儿，年龄（8.2±3.7）岁；对照组纳入28例健康儿童，年龄（7.6±2.7）岁。与对照组比较，活动期SJIA患儿的NLRP3在mRNA水平无显著改变，但蛋白表达量降低，同时IL-1β、IL-18浓度升高；SJIA患儿治疗2周后 IL-1β、IL-18、IL-2、IL-10、IFN-γ均降低，在治疗8周时IL-2、IFN-γ、IL-18仍低于治疗前水平；差异均有统计学意义（P<0.05）。 结论：SJIA中IL-1β和IL-18可能不是通过NLRP3炎症小体进行调控的。IL-1β和IL-18有潜力作为SJIA疾病活动的监测指标。

关键词: NLRP3炎症小体, 全身型幼年特发性关节炎, IL-1β, IL-18

Abstract: Background: Systemic juvenile idiopathic arthritis (SJIA) has a high disability rate and there are currently no specific therapeutic drugs. The efficacy of new biologic drugs developed for IL-1 or IL-6 monoclonal antibodies in some patients is not satisfactory. Further research on the pathogenesis is urgently needed to explore new treatment strategies. Objective: To explore the role of NLRP3 inflammasome and related inflammatory mediators in the pathogenesis of SJIA. Design: Case-control study. Methods: The children with SJIA in the active period were included, and the healthy children who went to the hospital for physical examination during the same period were the control group. Peripheral venous blood samples were collected from children with SJIA before glucocorticoid therapy, at 2 weeks and 8 weeks after treatment, and from healthy children during physical examination, and then peripheral blood mononuclear cells (PBMCs) were extracted. The mRNA and protein expression levels of NLRP3 and related inflammatory mediators were detected by Quantitative Rea-time-PCR (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), and Western blotting, respectively. Main outcome measures: Expression levels of NLRP3 and related inflammatory mediators. Results: A total of 33 children with SJIA were enrolled, aged (8.2±3.7) years. There were 28 healthy children, aged (7.6±2.7) years. Compared with healthy children, in active SJIA children there was no significant change in the mRNA level of NLRP3, but the protein expression decreased and the concentrations of IL-1β and IL-18 increased. After 2 weeks of treatment, the level of IL-1β, IL-18, IL-2, IL-10 and IFN-γ in children with SJIA all decreased, and at the 8th week of treatment, the level of IL-2, IFN-γ and IL-18 were still lower than those before treatment. The differences were statistically significant (P<0.05). Conclusion: In SJIA, IL-1β and IL-18 may not be regulated through NLRP3 inflammasomes. IL-1β and IL-18 can be used as monitoring indicators of SJIA disease activity.

Key words: NLRP3 inflammasome, Systemic juvenile idiopathic arthritis, IL-1β, IL-18

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