Zheng Qiu-Han, Zhai Ye, Wang Ying-Hang, Pan Zhi
Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun, China.
College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, China.
Front Immunol. 2025 Aug 18;16:1633406. doi: 10.3389/fimmu.2025.1633406. eCollection 2025.
Rheumatoid Arthritis (RA) is an autoimmune disease caused by many factors, with a high disability rate, unsatisfactory clinical treatment effect, and unclear pathogenesis. The oxygen level in the joint cavity is significantly reduced, and the hypoxic microenvironment has become a key factor in the pathogenesis and progression of RA. Based on the latest research developments, this review delves into the structure and main functions of the key factor HIF in the hypoxic microenvironment, and expounds the main regulatory mechanisms of HIF. The effect of the hypoxic microenvironment on the pathological changes of RA was analyzed, especially how hypoxia affects the signal transduction of related molecules and cells, thus aggravating the occurrence and development of RA. In addition, the review also discusses emerging therapeutic strategies aimed at targeting the hypoxic pathways, including HIF-1α inhibitors, Hyperbaric oxygen therapy, and the application of traditional Chinese medicine. By providing a comprehensive overview of the interplay between RA and the hypoxic microenvironment, this review aims to provide new perspectives on the underlying mechanisms of RA and provide a theoretical basis for the development of therapeutic drugs to improve the hypoxic microenvironment of RA.
类风湿关节炎（RA）是一种由多种因素引起的自身免疫性疾病，致残率高，临床治疗效果不理想，发病机制尚不明确。关节腔内氧水平显著降低，缺氧微环境已成为RA发病机制和病情进展的关键因素。基于最新研究进展，本综述深入探讨了缺氧微环境中关键因子缺氧诱导因子（HIF）的结构和主要功能，并阐述了HIF的主要调控机制。分析了缺氧微环境对RA病理变化的影响，特别是缺氧如何影响相关分子和细胞的信号转导，从而加重RA的发生和发展。此外，本综述还讨论了针对缺氧途径的新兴治疗策略，包括HIF-1α抑制剂、高压氧治疗和中药应用。通过全面概述RA与缺氧微环境之间的相互作用，本综述旨在为RA的潜在机制提供新的视角，并为开发改善RA缺氧微环境的治疗药物提供理论依据。
