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程序性细胞死亡在类风湿关节炎中的研究进展

韩珂^1,2, 丁子夏³, 何晓宇¹, 吴天宇⁴, 孟宇航³, 杜邦³, 张小楠^1,5,*

¹蚌埠医科大学心脑血管疾病基础与临床重点实验室，蚌埠 233000；²蚌埠医科大学人体解剖学教研室，蚌埠 233000；³蚌埠医科大学临床医学院，蚌埠 233000；⁴蚌埠医科大学公共卫生学院，蚌埠 233000；⁵蚌埠医科大学病理生理学教研室，蚌埠 233000

摘要

类风湿关节炎(rheumatoid arthritis, RA)是一种慢性炎性系统性疾病，其病因仍不明确。该疾病以对称性手、足等远端小关节的侵袭性炎症为主要病理特征，可导致关节畸形及功能丧失，且常伴肺、心脏等器官的受累。目前用于治疗RA的抗风湿药虽然能够改善病情，但仍存在明显毒副作用，亟待进一步的优化。因此，深入解析 RA 发生和发展机制对新药物靶点的开发至关重要。程序性细胞死亡(programmed cell death, PCD)在RA中的重要作用受到了广泛关注，特别是在滑膜细胞、免疫细胞和骨细胞中，PCD的失调现象尤为显著。本文综述了PCD的多种形式，包括凋亡、NETosis、自噬、焦亡、坏死性凋亡、铁死亡、铜死亡等在RA中的调控作用，并探讨了它们在成纤维滑膜细胞、免疫细胞和骨细胞等中的调控作用。这些研究不仅为优化RA临床治疗方案提供了重要理论依据，也为新靶点药物的研发指明了方向。

关键词： 类风湿关节炎; 程序性细胞死亡; 调控作用

The research development of programmed cell death in rheumatoid arthritis

HAN Ke^1,2, DING Zi-Xia³, HE Xiao-Yu¹, WU Tian-Yu⁴, MENG Yu-Hang³, DU Bang³, ZHANG Xiao-Nan^1,5,*

¹Key Laboratory of Cardiovascular and Cerebrovascular Diseases, Bengbu Medical University, Bengbu 233030, China ；²Department of Human Anatomy, Bengbu Medical University, Bengbu 233030, China ；³Clinical Medicine Department, Bengbu Medical University, Bengbu 233030, China ；⁴School of Public Health, Bengbu Medical University, Bengbu 233030, China；⁵Department of Pathophysiology, Bengbu Medical University, Bengbu 233030, China

Abstract

The etiology of rheumatoid arthritis (RA), a chronic inflammatory systemic disease, remains unclear. It is characterized by symmetrical and invasive joint inflammation, primarily affecting distal small joints such as those in the hands and feet. This inflammation can lead to joint deformity and loss of function, and often accompanied by involvement of extra-articular organs like the lungs and heart. Currently, anti-rheumatic drugs only provide symptom improvement but have toxic side effects that require optimization. Therefore, it is crucial to thoroughly analyze the mechanisms underlying RA development for the identification of new drug targets. Programmed cell death (PCD) has been extensively studied in recent years and proved to be one of the key pathogenic factors in RA. Dysregulation of PCD is particularly evident in synoviocytes, immune cells, and osteocytes. This review summarizes various forms of PCD including apoptosis, NETosis, autophagy, pyroptosis, necroptosis, ferroptosis, cuproptosis, as well as their regulatory roles in fibroblast synoviocytes, immune cells and osteocytes. These findings hold significant theoretical implications for optimizing clinical treatment options for RA and developing new target drugs.

Key words: rheumatoid arthritis; programmed cell death; regulatory roles

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通讯作者：张小楠　　E-mail:

引用本文：

韩珂, 丁子夏, 何晓宇, 吴天宇, 孟宇航, 杜邦, 张小楠. 程序性细胞死亡在类风湿关节炎中的研究进展[J]. 生理学报 2024; 76 (5): 827-840.

HAN Ke, DING Zi-Xia, HE Xiao-Yu, WU Tian-Yu, MENG Yu-Hang, DU Bang, ZHANG Xiao-Nan. The research development of programmed cell death in rheumatoid arthritis. Acta Physiol Sin 2024; 76 (5): 827-840 (in Chinese with English abstract).