Yoshida Akiko, Murakami Kosaku, Tsukamoto Hirotake, Hotta Yunhong, Nakayama Yoichi, Saito Rintaro, Shirakashi Mirei, Tsuji Hideaki, Hiwa Ryosuke, Akizuki Shuji, Nakashima Ran, Yoshifuji Hajime, Onishi Akira, Tanaka Masao, Mimori Tsuneyo, Morinobu Akio
Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Division of Clinical Immunology and Cancer Immunotherapy, Center for Cancer Immunotherapy and Immunobiology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Mod Rheumatol. 2025 Jul 5;35(4):665-676. doi: 10.1093/mr/roaf019.
Polyunsaturated fatty acids (PUFAs) are healthy fats that contain a double carbon bond. They are made up of omega (ω)-3 and ω-6 PUFAs, where ω-3 PUFAs exhibit beneficial effects, such as the suppression of cardiovascular events and the improvement of abnormal lipid metabolism. However, their effects on rheumatoid arthritis (RA) are unclear. Epoxy fatty acids, which are intermediate metabolites of ω-6 and ω-3 PUFAs, are formed through the action of cytochrome P and possess anti-inflammatory properties. However, they are quickly converted into their inactive forms by soluble epoxide hydrolase.
The protective effects of ω-3 and ω-6 PUFAs on arthritic symptoms with or without soluble epoxide hydrolase inhibitors (sEHis) were investigated in a collagen-induced arthritis mouse model.
The group treated with a combination of ω-3 PUFAs and sEHi showed a marked inhibition of arthritis compared to the other groups. Analysis of the faecal flora before the onset of arthritis showed an inverse correlation between the arthritis score and the relative abundance of Lactococcus, suggesting that changes in the intestinal flora in the preclinical stage may influence the onset of arthritis.
This study highlights the potential of ω-3 PUFAs combined with sEHi as the novel protective effect for RA.
多不饱和脂肪酸（PUFAs）是含有碳双键的健康脂肪。它们由ω（ω）-3和ω-6多不饱和脂肪酸组成，其中ω-3多不饱和脂肪酸具有有益作用，如抑制心血管事件和改善脂质代谢异常。然而，它们对类风湿性关节炎（RA）的影响尚不清楚。环氧脂肪酸是ω-6和ω-3多不饱和脂肪酸的中间代谢产物，通过细胞色素P的作用形成，具有抗炎特性。然而，它们会被可溶性环氧化物水解酶迅速转化为无活性形式。
在胶原诱导的关节炎小鼠模型中，研究了ω-3和ω-6多不饱和脂肪酸在有或没有可溶性环氧化物水解酶抑制剂（sEHis）情况下对关节炎症状的保护作用。
与其他组相比，用ω-3多不饱和脂肪酸和sEHi联合治疗的组对关节炎有明显抑制作用。关节炎发作前对粪便菌群的分析表明，关节炎评分与乳酸球菌的相对丰度呈负相关，这表明临床前期肠道菌群的变化可能会影响关节炎的发作。
本研究强调了ω-3多不饱和脂肪酸与sEHi联合使用对类风湿性关节炎具有新的保护作用的潜力。
