基于细胞焦亡探讨关节炎发病机制的研究进展

Research progress on pathogenesis of arthritis based on pyroptosis

关键词:  关节炎  细胞焦亡  NLRP3  IL-1  GSDMs  靶向药物

Key words:  arthritis  Pyroptosis  NLRP3  IL-1  GSDMs  Targeted drug

摘要:

关节炎是常见的炎性疾病,其临床特点表现为关节疼痛、肿胀及活动受限。据我国致残疾病调查数据显示:关节疾病位居第一,远高于心脑血管疾病,严重影响患者的生活质量和工作能力。最近的研究表明,以NLRP3炎性小体为主导的蛋白和因子在关节炎的病程中发挥关键作用:NLRP3炎性小体通过激活Caspase-1,促进其切割gasdermin D （GSDMD）和IL-1β和IL-18等炎症细胞因子,继而引发细胞焦亡,最终导致细胞裂解死亡。越来越多的研究表明细胞焦亡在关节炎疾病的发展中扮演着重要角色,因此,通过总结近年来与细胞焦亡相关的研究,对细胞焦亡在关节炎领域的研究进展进行评价和综合概述。

Abstract:

Arthritis is a prevalent inflammatory disease characterized by joint pain, swelling, and restricted mobility. In China, joint disorders rank as the leading cause of disability, surpassing cardiovascular and cerebrovascular diseases, with profound socioeconomic consequences due to reduced workforce productivity and diminished quality of life. Emerging evidence highlights the central role of NLRP3 inflammasome-mediated signaling pathways in driving arthritis progression. Mechanistically, inflammasome activation triggers caspase-1 proteolytic activation, leading to gasdermin D (GSDMD)-mediated membrane pore formation and release of pro-inflammatory cytokines including interleukin-1β (IL-1β) and IL-18, thereby inducing pyroptosis—a lytic inflammatory cell death process. An increasing body of research underscores the significant role of pyroptosis in the pathogenesis of arthritis. Therefore, this article aims to review recent studies on pyroptosis in the context of arthritis to synthesize current research advancements.