电针调控小胶质细胞AhR-SYK通路促进髓鞘碎片清除与髓鞘再生

doi:10.12066/j.issn.1007-2861.2731

上海大学学报(自然科学版) ›› 2026, Vol. 32 ›› Issue (3): 388-401.doi: 10.12066/j.issn.1007-2861.2731

• 生物工程 • 上一篇

电针调控小胶质细胞AhR-SYK通路促进髓鞘碎片清除与髓鞘再生

王靓¹, 吴帅², 宁显会², 张童童², 吴心怡², 朱¹, 王雨萌¹, 周艺³, 汪军¹

1. 复旦大学基础医学院, 上海 200032;
2. 复旦大学附属中山医院, 上海 200032;
3. 94826部队门诊部, 上海 200000

收稿日期:2026-02-02 发布日期:2026-07-04
通讯作者: 汪军(1973—),女,教授,研究方向为针刺与中药改善神经退行性疾病的神经免疫机制. E-mail:jwangf@shmu.edu.cn
基金资助:
国家自然科学基金面上资助项目(82474635)

Regulation of microglial AhR-SYK pathway by electroacupuncture to promote myelin debris clearance and remyelination

WANG Liang¹, WU Shuai², NING Xianhui², ZHANG Tongtong², WU Xinyi², ZHU Zhe¹, WANG Yumeng¹, ZHOU Yi³, WANG Jun¹

1. School of Basic Medical Sciences, Fudan University, Shanghai 200032, China;
2. Zhongshan Hospital, Fudan University, Shanghai 200032, China;
3. Outpatient Department of Unit 94826, Shanghai 200000, China

Received:2026-02-02 Published:2026-07-04

摘要/Abstract

摘要： 为了探讨电针(electroacupuncture,EA)调控小胶质细胞芳香烃受体-脾酪氨酸激酶(aryl hydrocarbon receptor-spleen tyrosine kinase,AhR-SYK)通路对双环己酮草酰二腙(cuprizone,CPZ)诱导的脱髓鞘小鼠髓鞘碎片清除与再髓鞘化的影响,运用0.3% CPZ饲喂C57BL/6J小鼠,构建脱髓鞘模型.通过行为学、免疫荧光(immunofluorescence,IF)、透射电子显微镜(transmission electron microscope,TEM)、定量反转录聚合酶链反应(quantitative reverse transcription polymerase chain reaction,qRT-PCR)及Western blot,评估了脱髓鞘程度、炎症反应及AhR-SYK通路表达.结果显示:EA显著缩短了CPZ小鼠通过平衡木的时间,并延长了转棒潜伏期;显著上调了胼胝体中髓鞘碱性蛋白(myelin basic protein,MBP)的表达及有髓轴突的比例;上调了AhR与SYK的表达,降低了降解型髓鞘碱性蛋白(degraded MBP,dMBP)的荧光强度及脂质沉积;下调了Nos2、IL-1b等促炎因子.由此可知,EA可能通过激活AhR-SYK通路,增强小胶质细胞对髓鞘碎片的清除并减轻神经炎症,进而促进髓鞘再生与运动功能恢复.

关键词: 多发性硬化, 再髓鞘化, 小胶质细胞, 芳香烃受体, 电针, 吞噬作用

Abstract: To investigate the effect of electroacupuncture (EA) on myelin debris clearance and remyelination in cuprizone (CPZ)-induced demyelinated mice through regulating the microglial aryl hydrocarbon receptor-spleen tyrosine kinase (AhR-SYK) pathway, a demyelination model was established by feeding C57BL/6J mice with 0.3% CPZ. Behavioral tests, immunofluorescence (IF), transmission electron microscope (TEM), quantitative reverse transcription polymerase chain reaction (qRT-PCR), and Western blot were used to evaluate the degree of demyelination, inflammatory responses, and expression of the AhR-SYK pathway. The results showed that EA significantly shortened the beam walking time and prolonged the rotarod latency of CPZ mice. It significantly upregulated the expression of myelin basic protein (MBP) and the proportion of myelinated axons in the corpus callosum, upregulated the expressions of AhR and SYK, reduced the fluorescence intensity of degraded MBP (dMBP) and lipid deposition, and downregulated the levels of pro-inflammatory cytokines such as Nos2 and IL-1β. Therefore, it was concluded that EA might promote remyelination and motor function recovery by activating the AhR-SYK pathway to enhance microglial clearance of myelin debris and attenuate neuroinflammation.

Key words: multiple sclerosis (MS), remyelination, microglia, aryl hydrocarbon receptor (AhR), electroacupuncture (EA), phagocytosis

中图分类号:

王靓, 吴帅, 宁显会, 张童童, 吴心怡, 朱, 王雨萌, 周艺, 汪军. 电针调控小胶质细胞AhR-SYK通路促进髓鞘碎片清除与髓鞘再生[J]. 上海大学学报(自然科学版), 2026, 32(3): 388-401.

WANG Liang, WU Shuai, NING Xianhui, ZHANG Tongtong, WU Xinyi, ZHU Zhe, WANG Yumeng, ZHOU Yi, WANG Jun. Regulation of microglial AhR-SYK pathway by electroacupuncture to promote myelin debris clearance and remyelination[J]. Journal of Shanghai University（Natural Science Edition）, 2026, 32(3): 388-401.

参考文献

[1] Reich D S, Lucchinetti C F, Calabresi P A. Multiple sclerosis [J]. N Engl J Med, 2018, 378(2): 169-180.
[2] Olsson T, Barcellos L F, Alfredsson L. Interactions between genetic, lifestyle and environmental risk factors for multiple sclerosis [J]. Nat Rev Neurol, 2017, 13(1): 25-36.
[3] Marcus R. What is multiple sclerosis? [J]. JAMA, 2022, 328(20): 2078.
[4] The L N. Multiple sclerosis under the spotlight [J]. Lancet Neurol, 2021, 20(7): 497.
[5] Correale J, Marrodan M, Ysrraelit M C. Mechanisms of neurodegeneration and axonal dysfunction in progressive multiple sclerosis [J]. Biomedicines, 2019, 7(1): 7010014.
[6] Saab A S, Nave K. Myelin dynamics: protecting and shaping neuronal functions [J]. Curr Opin Neurobiol, 2017, 47: 104-112.
[7] Schirmer L, Mobius W, Zhao C, et al. Oligodendrocyte-encoded Kir4.1 function is required for axonal integrity [J]. Elife, 2018(7): e36428-e36428.
[8] Yang C, Wang Y, Hua M, et al. Aryl hydrocarbon receptor: from pathogenesis to therapeutic targets in aging-related tissue fibrosis [J]. Ageing Res Rev, 2022, 79: 101662.
[9] Zhang W, Xie H Q, Li Y, et al. The aryl hydrocarbon receptor: a predominant mediator for the toxicity of emerging dioxin-like compounds [J]. J Hazard Mater, 2022, 426: 128084.
[10] Wang Y, Sun J, Zhu K, et al. Microglial aryl hydrocarbon receptor enhances phagocytic function via SYK and promotes remyelination in the cuprizone mouse model of demyelination [J]. Journal of Neuroinflammation, 2023, 20(1): 83.
[11] Sen M K, Mahns D A, Coorssen J R, et al. Behavioural phenotypes in the cuprizone model of central nervous system demyelination [J]. Neurosci Biobehav Rev, 2019, 107: 23-46.
[12] Vega-Riquer J M, Mendez-Victoriano G, Morales-Luckie R A, et al. Five decades of cuprizone, an updated model to replicate demyelinating diseases [J]. Curr Neuropharmacol, 2019, 17(2): 129-141.
[13] Zhan J, Mann T, Joost S, et al. The cuprizone model: dos and do nots [J]. Cells, 2020, 9(4): 9040843.
[14] Ludwin S K. Central nervous system demyelination and remyelination in the mouse: an ultrastructural study of cuprizone toxicity [J]. Lab Invest, 1978, 39(6): 597-612.
[15] Zhu K, Sun J, Kang Z, et al. Electroacupuncture promotes remyelination after cuprizone treatment by enhancing myelin debris clearance [J]. Front Neurosci, 2016, 10: 613.
[16] Neumann H, Kotter M R, Franklin R J M. Debris clearance by microglia: an essential link between degeneration and regeneration [J]. Brain, 2009, 132: 288-295.
[17] Xia Y. Advanced acupuncture research: from bench to bedside [M]. Cham: Springer, 2022.
[18] Ding Y, Shi X. Controlled research on multiple sclerosis treated with electroacupuncture and acupoint injection [J]. Chinese Acupuncture & Moxibustion, 2013, 33(9): 793-795.
[19] Wang C, Chen Z, Wang L, et al. Relapsing-remitting multiple sclerosis at remission stage treated with acupuncture: a randomized controlled trial [J]. Chinese Acupuncture & Moxibustion, 2017, 37(6): 576-580.
[20] Lloyd A F, Miron V E. The pro-remyelination properties of microglia in the central nervous system [J]. Nat Rev Neurol, 2019, 15(8): 447-458.
[21] Berghoff S A, Spieth L, Sun T, et al. Microglia facilitate repair of demyelinated lesions via post-squalene sterol synthesis [J]. Nat Neurosci, 2021, 24(1): 47-60.
[22] Patani R, Balaratnam M, Vora A, et al. Remyelination can be extensive in multiple sclerosis despite a long disease course [J]. Neuropathol Appl Neurobiol, 2007, 33(3): 277-287.
[23] Voss E V, Skuljec J, Gudi V, et al. Characterisation of microglia during de- and remyelination: can they create a repair promoting environment? [J]. Neurobiol Dis, 2012, 45(1): 519-528.
[24] Masuda T, Sankowski R, Staszewski O, et al. Author correction: spatial and temporal heterogeneity of mouse and human microglia at single-cell resolution [J]. Nature, 2019, 568(7751): E4.
[25] Franklin R J M, Ffrench-Constant C. Regenerating CNS myelin: from mechanisms to experimental medicines [J]. Nat Rev Neurosci, 2017, 18(12): 753-769.
[26] Stangel M, Kuhlmann T, Matthews P M, et al. Achievements and obstacles of remyelinating therapies in multiple sclerosis [J]. Nat Rev Neurol, 2017, 13(12): 742-754.
[27] Rawji K S, Kappen J, Tang W, et al. Deficient surveillance and phagocytic activity of myeloid cells within demyelinated lesions in aging mice visualized by ex vivo live multiphoton imaging [J]. J Neurosci, 2018, 38(8): 1973-1988.
[28] Healy L M, Perron G, Won S, et al. MerTK is a functional regulator of myelin phagocytosis by human myeloid cells [J]. J Immunol, 2016, 196(8): 3375-3384.
[29] Zou Z, Sun J, Kang Z, et al. Tyrosine kinase receptors Axl and MerTK mediate the beneficial effect of electroacupuncture in a cuprizone-induced demyelinating model [J]. Evid Based Complement Alternat Med, 2020(7): 3205176.
[30] Tohyama Y, Yamamura H. Protein tyrosine kinase, Syk: a key player in phagocytic cells [J]. J Biochem, 2009, 145(3): 267-273.
[31] Berton G, MocSai A, Lowell C A. Src and Syk kinases: key regulators of phagocytic cell activation [J]. Trends Immunol, 2005, 26(4): 208-214.
[32] Jakus Z, Simon E, Balazs B, et al. Genetic deficiency of Syk protects mice from autoantibodyinduced arthritis [J]. Arthritis Rheum, 2010, 62(7): 1899-1910.
[33] Podolanczuk A, Lazarus A H, Crow A R, et al. Of Mice and Men: an open-label pilot study for treatment of immune thrombocytopenic purpura by an inhibitor of Syk [J]. Blood, 2009, 113(14): 3154-3160.
[34] Ennerfelt H, Frost E L, Shapiro D A, et al. SYK coordinates neuroprotective microglial responses in neurodegenerative disease [J]. Cell, 2022, 185(22): 4135-4152.

电针调控小胶质细胞AhR-SYK通路促进髓鞘碎片清除与髓鞘再生

Regulation of microglial AhR-SYK pathway by electroacupuncture to promote myelin debris clearance and remyelination

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