利用网络毒理学方法，研究三氯生加剧类风湿关节炎的分子机制。

Abstract

This study comprehensively employed network toxicology and experimental validation to systematically investigate the potential mechanisms by which triclosan (TCS) exacerbates rheumatoid arthritis (RA). Through multi-database screening, 173 common targets between TCS and RA were obtained. Combined with protein-protein interaction (PPI) network analysis and five machine learning algorithms, eight core hub genes (AR, CDKN1A, IGF1R, JAK2, JUN, MAPK8, MYC, and PARP1) were identified. Enrichment analysis indicated that TCS primarily interferes with signalling pathways, such as JAK-STAT, cellular senescence, and mitophagy. In vitro experiments demonstrated that TCS induces macrophage senescence and polarisation toward the M1 phenotype, promotes the expression of inflammatory cytokines, and inhibits mitophagy, leading to the accumulation of mitochondrial reactive oxygen species (ROS), loss of mitochondrial membrane potential, and impaired mitochondrial function, thereby exacerbating the inflammatory response. This study reveals that TCS may disrupt immune-metabolic homeostasis through multi-target, multi-pathway mechanisms to promote the onset and progression of RA, providing a new theoretical basis for understanding its environmental toxicity and for the prevention and treatment of RA.