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通过调节脂肪酸代谢减轻实验性自身免疫性脑脊髓炎的Th17/Treg免疫失衡

Alleviates Th17/Treg Immune Imbalance of Experimental Autoimmune Encephalomyelitis by Regulating the Fatty Acids Metabolism.

作者信息

Wu Lulu, Xu Haoyou, Xia Hui, Peng Lilin, Qin Lulu, Gong Qian, Zhao Min, Wu Zhibing, Zhao Yuanqi, Zheng Zequan

机构信息

The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People's Republic of China.

The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People's Republic of China.

出版信息

Drug Des Devel Ther. 2025 Jun 3;19:4755-4776. doi: 10.2147/DDDT.S510620. eCollection 2025.

Abstract

BACKGROUND

Multiple sclerosis (MS) is one of the leading causes of disability among young people, and the immune imbalance between T helper cell 17 (Th17) and regulatory T cells (Tregs) plays a crucial role in its pathogenesis. Currently, MS treatment relies significantly on immunosuppressive drugs or glucocorticoids, which often have side effects and limitations in efficacy. Sheng-Jiang powder (SJP), a traditional Chinese medicine formula, has demonstrated anti-inflammatory effects and may offer a novel therapeutic option for MS.

AIM

This study aimed to investigate the therapeutic efficacy and underlying mechanism of SJP in myelin oligodendrocyte glycoprotein 35-55 (MOG35-55)-induced experimental autoimmune encephalomyelitis (EAE) mice.

METHODS

The efficacy of SJP was assessed using the MOG35-55-induced EAE model. Disease severity was monitored based on the clinical symptoms, body weight, and pathological damage. Furthermore, Th17/Treg balance in the peripheral and central immune systems was assessed. Metabolomic analysis was performed to detect differential metabolites in serum, and the effects of fatty acids on the lipoxygenase (LOX) metabolic pathway were investigated.

RESULTS

SJP alleviated MOG35-55-induced EAE symptoms and histological damage, restored the peripheral Th17/Treg immune balance, decreased pro-inflammatory cytokine levels, and increased anti-inflammatory cytokine levels. SJP intervention also influenced omega-3 polyunsaturated fatty acid (PUFA) metabolism and absorption in EAE mice, promoting an anti-inflammatory process associated with 12/15-lipoxygenase(12/15-LOX) upregulation and 5-lipoxygenase(5-LOX) downregulation.

CONCLUSION

This study suggests that SJP is a viable treatment option for MS, and traditional Chinese medicine therapies for autoimmune diseases will continue to be developed.

摘要

背景

多发性硬化症(MS)是年轻人致残的主要原因之一,辅助性T细胞17(Th17)与调节性T细胞(Tregs)之间的免疫失衡在其发病机制中起关键作用。目前,MS治疗主要依赖免疫抑制药物或糖皮质激素,这些药物往往有副作用且疗效有限。升降散(SJP)是一种中药配方,已显示出抗炎作用,可能为MS提供一种新的治疗选择。

目的

本研究旨在探讨升降散对髓鞘少突胶质细胞糖蛋白35-55(MOG35-55)诱导的实验性自身免疫性脑脊髓炎(EAE)小鼠的治疗效果及潜在机制。

方法

使用MOG35-55诱导的EAE模型评估升降散的疗效。根据临床症状、体重和病理损伤监测疾病严重程度。此外,评估外周和中枢免疫系统中的Th17/Treg平衡。进行代谢组学分析以检测血清中的差异代谢物,并研究脂肪酸对脂氧合酶(LOX)代谢途径的影响。

结果

升降散减轻了MOG35-55诱导的EAE症状和组织学损伤,恢复了外周Th17/Treg免疫平衡,降低了促炎细胞因子水平,提高了抗炎细胞因子水平。升降散干预还影响了EAE小鼠体内ω-3多不饱和脂肪酸(PUFA)的代谢和吸收,促进了与12/15-脂氧合酶(12/15-LOX)上调和5-脂氧合酶(5-LOX)下调相关的抗炎过程。

结论

本研究表明升降散是MS的一种可行治疗选择,针对自身免疫性疾病的中医治疗将不断发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76bf/12145100/564cb0d96460/DDDT-19-4755-g0001.jpg

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