Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by progressive joint destruction and high disability rates. Moxibustion, a traditional Chinese medicine therapy with a long history of use in RA management, has attracted increasing clinical attention. Although previous studies have explored the mechanisms underlying the efficacy of moxibustion in RA, its lipidomic mechanisms remain unclear. Therefore, this study aimed to elucidate the lipidomic mechanisms of moxibustion by integrating broad-spectrum targeted lipidomics and eicosanoid-targeted lipidomics to identify key lipid metabolites associated with its therapeutic effects. Thirty-two male Sprague–Dawley rats were randomly assigned to four groups (n = 8 per group): control, model, moxibustion control, and moxibustion model groups. The collagen-induced arthritis (CIA) model was established by two rounds of immunization. Moxibustion was applied bilaterally at “Zusanli (ST 36)” and “Shenshu (BL23)” for 10 minutes per acupoint (40 minutes per session). Treatment was administered once daily for six consecutive days per cycle, for three cycles, with a one-day interval between cycles. After three weeks of treatment, therapeutic effects were evaluated based on body weight, paw volume, arthritis index (AI) score, visceral indices, and histopathological examination. Serum lipid profiles were analyzed to identify differential metabolites and metabolic pathways associated with moxibustion. Compared with the control group, rats in the model group exhibited poor general condition, significant body weight loss, and marked increases in paw volume and AI score ( P < 0.05), as well as significantly elevated visceral indices ( P < 0.05). In contrast, moxibustion treatment significantly improved general condition, restored body weight, and reduced paw volume, AI score, and visceral indices compared with the model group ( P < 0.05). Histopathological examination revealed marked synovial hyperplasia, inflammatory cell infiltration, and cartilage destruction in the ankle joints of the model group, whereas these pathological changes were significantly alleviated by moxibustion. Lipidomic analysis identified 81 differential metabolites between the model and control groups, and moxibustion ameliorated disruptions in the arachidonic acid (ARA) and linoleic acid (LA) pathways. Broad-spectrum targeted lipidomics showed that moxibustion regulated 19 lipid species. Eicosanoid-targeted profiling further demonstrated that, under pathological conditions, moxibustion modulated eight of these lipids to attenuate proinflammatory mediators, whereas under physiological conditions, it adjusted six lipids to maintain lipid homeostasis. CIA rats exhibited significant disturbances in lipid metabolism, mainly involving the ARA and LA pathways. Moxibustion effectively regulated broad-spectrum lipid classes and specific eicosanoid mediators, thereby alleviating inflammation under pathological conditions and contributing to physiological homeostasis. 类风湿关节炎 (RA) 是一种广泛存在的疾病, 其特点是致残率高.艾灸是一种具有悠久历史的传统中医疗法, 用于治疗RA, 并且越来越受到临床关注.尽管已有研究探讨了艾灸治疗RA的潜在机制, 但本研究特别聚焦于揭示其脂质组学机制.本研究首次整合广谱靶向脂质组学与类花生酸靶向脂质组学, 通过鉴定关键脂质代谢物, 阐明艾灸治疗RA的作用机制. 32只雄性SD大鼠被分为四组:正常组,正常艾灸组,模型组和模型艾灸组, 每组8只.通过两次免疫诱导建立大鼠CIA模型.艾灸干预选取双侧“足三里”和“肾俞”穴, 每穴艾灸10分钟, 每日1次, 每次共40分钟.以6天为1个疗程, 共治疗3个疗程, 疗程间休息1天.经过3周的艾灸治疗后, 通过体重,趾体积,关节炎指数 (AI) 评分,脏器指数和组织病理学评估治疗效果.通过分析血清脂质谱来鉴定与艾灸相关的差异代谢物和代谢通路. 与正常组相比, 模型组大鼠一般状况差, 体重显著下降, 足容积及关节炎评分显著升高 ( P < 0.05) , 内脏指数显著增加 ( P < 0.05) .与模型组相比, 艾灸组大鼠一般状况明显改善, 体重回升, 足容积及关节炎评分均显著降低 ( P < 0.05) , 内脏指数亦显著下降 ( P < 0.05) .组织病理学显示, 模型组踝关节滑膜增生,炎性细胞浸润及软骨破坏明显;艾灸组上述病理改变显著减轻.脂质组学结果发现模型组与正常组间存在81种差异代谢物, 艾灸可逆转花生四烯酸和亚油酸通路中的紊乱.广谱靶向分析显示艾灸能够调控19种脂质水平.类花生酸靶向分析进一步表明, 艾灸在病理状态下调节8种脂质以降低促炎物质, 生理状态下调节6种脂质以维持脂质平衡. 本研究发现 (CIA) 大鼠存在显著的脂质代谢紊乱, 主要涉及花生四烯酸和亚油酸通路.艾灸能够调控广谱脂质类别及特定类花生酸介质, 在病理状态下减轻炎症, 同时在生理状态下发挥一定保健作用.
Ying et al. (Sun,) studied this question.