中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2026, Vol. 21 ›› Issue (6): 2563-2572.doi: 10.4103/NRR.NRR-D-24-01093

• 原著:退行性病与再生 • 上一篇    下一篇

枸杞多糖（枸杞提取物）可改善多发性硬化小鼠模型中致病性CD4+T细胞活化

  

  • 出版日期:2026-06-15 发布日期:2026-04-18

Effects of Lycium barbarum polysaccharide on the activation of pathogenic CD4+ T cells in a mouse model of multiple sclerosis

Mengdi Guo1, #, Guozhen Deng1, #, Bin Huang1, #, Zhiyong Lin1, Xue Yang1, Linglin Dong1, Zilin Wang2, Yi Guo1, Ming Yi1, Weiyan Wang1, *, Mei-Ling Jiang3, *, Cun-Jin Zhang1, *   

  1. 1Department of Neurology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan Province, China; 
    2Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China; 
    3Department of Science and Technology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan Province, China
  • Online:2026-06-15 Published:2026-04-18
  • Supported by:
    This study was supported by the National Natural Science Foundational of China, Nos. U24A20692 (to CJZ), 82371355 (to CJZ), and 82101414 (to MH); National Natural Science Foundational of China for Excellent Young Scholars, No. 82022019(to CJZ); Sichuan Special Fund for Distinguished Young Scholars, No. 24NSFJQ0052 (to CJZ); The Innovation and Entrepreneurial Team of Sichuan Tianfu Emei Program, No. CZ2024018 (to CJZ); Funding for Distinguished Young Scholars of Sichuan Provincial People’s Hospital, No. 30420230005; Funding for Distinguished Young Scholars of University of Electronic Science and Technology of China, No. A1098531023601381 (to CJZ); Sichuan Science and Technology Support Project, No. 2023YFS0212 (to BH); and Project of Sichuan Provincial Health Commission, No. 19PJ265 (to LD).

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摘要：

多发性硬化是一种严重的自身免疫性疾病，主要由致病性CD4+亚群介导。尽管在多发性硬化治疗已取得了一些进展，但仍然迫切需要更有效、更安全的治疗方法。此次实验给予实验性自身免疫性脑脊髓炎（一种多发性硬化的动物模型）小鼠灌胃枸杞多糖，然后评估枸杞多糖对体内外致病性CD4+T细胞活化的影响。结果显示，枸杞多糖显著减轻了实验性自身免疫性脑脊髓炎严重程度，即减轻脱髓鞘和神经炎症。枸杞多糖还减少了外周白细胞浸润中枢神经系统，并抑制促炎细胞因子的表达。枸杞多糖可通过抑制Th1/Th17分化和促进Treg扩增来调节致病性CD4+T细胞反应。值得注意的是，未见枸杞多糖的任何副作用，即枸杞多糖存在长期安全性和耐受性。RNA测序结果表明，枸杞多糖抑制T 细胞活化和分化的重要调节因子激活蛋白1表达，这可通过激活蛋白1阻断后 Th1/Th17 反应抑制的逆转得到证实。上述结果说明，枸杞多糖具有作为CD4+T细胞相关自身免疫性或炎症性疾病（如多发性硬化）治疗药物的潜力。


https://orcid.org/0000-0003-0384-8958 (Weiyan Wang); https://orcid.org/0000-0001-7996-7246 (Cun-Jin Zhang)

关键词: 枸杞糖肽, 多发性硬化, 实验性自身免疫性脑脊髓炎, 致病性CD4+T细胞, Th1/Th17分化, 三重极化, AP-1信号通路, NLRP3炎症小体, NF-κB信号通路, 神经炎症

Abstract: Multiple sclerosis is a severe autoimmune disorder that is mainly mediated by pathogenic cluster of CD4+ T cell subsets. Despite advancements in the management of multiple sclerosis, there is a critical need for more effective and safer treatments. In the present study, we administered Lycium barbarum glycopeptide to a mouse model of experimental autoimmune encephalomyelitis—an animal model of multiple sclerosis—and evaluated its effects on pathogenic CD4+ T cell activation both in vivo and in vitro. Lycium barbarum glycopeptide significantly mitigated the clinical severity of experimental autoimmune encephalomyelitis, as demonstrated by reduced demyelination and neuroinflammation. Moreover, Lycium barbarum glycopeptide treatment decreased the infiltration of peripheral leukocytes into the central nervous system and suppressed pro-inflammatory cytokine expression. Lycium barbarum glycopeptide also modulated pathogenic CD4+ T cell activation by inhibiting T helper 1/T helper 17 cell differentiation while promoting regulatory T cell expansion. Notably, no side effects were observed, suggesting the long-term safety and tolerability of Lycium barbarum glycopeptide. Furthermore, RNA sequencing data indicated that Lycium barbarum glycopeptide inhibits activator protein-1, an essential regulator of T cell activation and differentiation. This finding was supported by the reversal of T helper/ T helper 17 cell response suppression upon AP-1 blockade. Collectively, these results highlight the potential of Lycium barbarum glycopeptide as an innovative therapeutic agent for CD4+ T cell-associated autoimmune or inflammatory diseases, such as multiple sclerosis. 

Key words: AP-1 signaling pathway, experimental autoimmune encephalomyelitis, Lycium barbarum glycopeptide, multiple sclerosis, neuroinflammation, nucelar factor-κB signaling pathway, NLRP3 inflammasome, pathogenic CD4+ T cells, T helper 1/T helper 17 cell differentiation, Treg polarization