基于微生物–肠–脑轴的针灸调控海马神经炎症治疗抑郁症的机制研究进展
Research Progress on the Mechanism of Acupuncture in Treating Depression by Regulating Hippocampal Neuroinflammation via the Microbiota-Gut-Brain Axis
DOI: 10.12677/tcm.2026.152084, PDF,    科研立项经费支持
作者: 陈凯歌, 杨雨石, 林婉瑜, 胡雨晴, 张丹妮：天津中医药大学管理学院，天津；王轶丹*：天津中医药大学中西医结合学院，天津
关键词: 抑郁症；针灸；微生物–肠–脑轴；海马；神经炎症；预防医学；Depressive Disorder； Acupuncture； Microbiota-Gut-Brain Axis； Hippocampus； Neuroinflammation； Preventive Medicine
摘要: 抑郁症是一种常见的精神疾病，病程长、复发率高，严重影响患者的生活质量。目前临床一线抗抑郁药物存在起效慢、副作用多、有效率不高等问题，亟需探索新的治疗策略。近年来研究表明，部分抑郁症患者存在显著的炎症特征，而微生物–肠–脑轴功能失调及其介导的神经炎症反应，被认为是抑郁症的重要病理生理基础。针灸作为一种有效的神经调节疗法，其通过干预微生物–肠–脑轴发挥抗抑郁作用的研究日益受到关注，是颇具前景的探索方向。本文主要综述了针灸通过调节肠道菌群与肠道屏障、抑制外周及中枢神经炎症，进而修复海马神经可塑性的潜在作用通路及相关研究进展，以期为临床转化和预防医学提供新思路。
Abstract: Major depressive disorder (MDD) is a prevalent mental illness characterized by a prolonged course, high recurrence rate, and significant impairment of quality of life. Current first-line antidepressants suffer from delayed onset, multiple side effects, and suboptimal efficacy, underscoring the need for novel therapeutic strategies. Recent studies reveal prominent inflammatory features in subsets of MDD patients, with microbiota-gut-brain axis (MGBA) dysfunction and its mediated neuroinflammation recognized as key pathophysiological mechanisms. Acupuncture, an effective neuromodulatory therapy, has gained attention for its antidepressant effects via MGBA intervention, representing a promising avenue. This review synthesizes the potential pathways and recent advances in acupuncture’s regulation of gut microbiota and barrier integrity, suppression of peripheral and central neuroinflammation, and restoration of hippocampal neuroplasticity, aiming to inform clinical translation and preventive approaches.
文章引用：陈凯歌, 杨雨石, 林婉瑜, 胡雨晴, 张丹妮, 王轶丹. 基于微生物–肠–脑轴的针灸调控海马神经炎症治疗抑郁症的机制研究进展[J]. 中医学, 2026, 15(2): 124-131. https://doi.org/10.12677/tcm.2026.152084

参考文献

[1] Vos, T., Lim, S.S., Abbafati, C., Abbas, K.M., Abbasi, M., Abbasifard, M., et al. (2020) Global Burden of 369 Diseases and Injuries in 204 Countries and Territories, 1990-2019: A Systematic Analysis for the Global Burden of Disease Study 2019. The Lancet, 396, 1204-1222. [Google Scholar] [CrossRef] 
[2] Malhi, G.S. and Mann, J.J. (2018) Depression. The Lancet, 392, 2299-2312. [Google Scholar] [CrossRef] 
[3] World Health Organization (2023) Depressive Disorder (Depression). https://www.who.int/news-room/fact-sheets/detail/depression
[4] Rush, A.J., Trivedi, M.H., Wisniewski, S.R., Nierenberg, A.A., Stewart, J.W., Warden, D., et al. (2006) Acute and Longer-Term Outcomes in Depressed Outpatients Requiring One or Several Treat-ment Steps: A STAR*D Report. American Journal of Psychiatry, 163, 1905-1917. [Google Scholar] [CrossRef] 
[5] Cipriani, A., Furukawa, T.A., Salanti, G., Chaimani, A., Atkinson, L.Z., Og-awa, Y., et al. (2018) Comparative Efficacy and Acceptability of 21 Antidepressant Drugs for the Acute Treatment of Adults with Ma-jor Depressive Disorder: A Systematic Review and Network Meta-analysis. The Lancet, 391, 1357-1366. [Google Scholar] [CrossRef] 
[6] Beurel, E., Toups, M. and Nemeroff, C.B. (2020) The Bidirectional Rela-tionship of Depression and Inflammation: Double Trouble. Neuron, 107, 234-256. [Google Scholar] [CrossRef] 
[7] Valkanova, V., Ebmeier, K.P. and Allan, C.L. (2013) CRP, IL-6 and Depres-sion: A Systematic Review and Meta-Analysis of Longitudinal Studies. Journal of Affective Disorders, 150, 736-744. [Google Scholar] [CrossRef] 
[8] Lanquillon, S. (2000) Cytokine Production and Treatment Response in Major De-pressive Disorder. Neuropsychopharmacology, 22, 370-379. [Google Scholar] [CrossRef] 
[9] Miller, A.H. and Raison, C.L. (2015) The Role of Inflammation in Depression: From Evolutionary Imperative to Modern Treatment Target. Nature Reviews Immunology, 16, 22-34. [Google Scholar] [CrossRef] 
[10] Borsini, A., Zunszain, P.A., Thuret, S. and Pariante, C.M. (2015) The Role of Inflammatory Cytokines as Key Modulators of Neurogenesis. Trends in Neurosciences, 38, 145-157. [Google Scholar] [CrossRef] 
[11] Wu, Q., Zhou, H.-J., Gong, L.-L., et al. (2025) Moringa Isothiocyanate-1 Modu-lates LPS-Induced Depressive-Like Behavior through the Microbiota-Gut-Brain Axis. Food Science and Human Wellness, 14, 519-530.
[12] Kelly, J.R., Kennedy, P.J., Cryan, J.F., Dinan, T.G., Clarke, G. and Hyland, N.P. (2015) Breaking down the Barriers: The Gut Microbiome, Intestinal Permeability and Stress-Related Psychiatric Disorders. Frontiers in Cellular Neuroscience, 9, Article No. 392. [Google Scholar] [CrossRef] 
[13] Martin, C.R., Osadchiy, V., Kalani, A. and Mayer, E.A. (2018) The Brain-Gut-Microbiome Axis. Cellular and Molecular Life Sciences, 75, 1321-1348.
[14] Maes, M., Kubera, M. and Leunis, J.C. (2012) The Gut-Brain Barrier in Major Depression: Intestinal Mucosal Dysfunction with an Increased Translocation of LPS from Gram-Negative Enterobacteria (Leaky Gut) Plays a Role in the Inflammatory Pathophysiology of Depression. Neuroendocrinology Letters, 33, 712-722.
[15] Armour, M., Smith, C., Wang, L., Naidoo, D., Yang, G., MacPherson, H., et al. (2019) Acupuncture for Depression: A Systematic Review and Meta-Analysis. Journal of Clinical Medicine, 8, Article No. 1140. [Google Scholar] [CrossRef] 
[16] 张樟进, 王伟, 孟智宏, 等. 电针联合西酞普兰治疗抑郁症的多中心随机对照研究[J]. 上海精神医学, 2012, 24(5): 264-269.
[17] Deadman, P., Al-Khafaji, M. and Baker, K. (2007) A Manual of Acupuncture. East Sussex: Journal of Chinese Medi-cine Publications, 1-675.
[18] Liu, S., Wang, Z., Su, Y., Qi, L., Yang, W., Fu, M., et al. (2021) A Neuroanatomical Basis for Electroacupuncture to Drive the Vagal-Adrenal Axis. Nature, 598, 641-645. [Google Scholar] [CrossRef] 
[19] Zhang, Y., et al. (2021) Inflammation and Acupuncture: A Review of the Ef-fects of Acupuncture on the Immune System. Inflammation Research, 70, 525-541.
[20] Zheng, P., Zeng, B., Liu, M., et al. (2016) The Gut Microbiome in Depressive Patients. Journal of Psychiatric Research, 83, 1-8.
[21] Li, Z., et al. (2021) The Effect of Acu-puncture on Major Depressive Disorder: A Systematic Review and Meta-Analysis of fMRI Studies. Frontiers in Psychiatry, 12, Article ID: 694038.
[22] 陶伟伟, 董宇, 刘立, 等. 基于“脑-肠”轴的肠道菌群影响抑郁症研究进展[J]. 南京中医药大学学报, 2019, 35(2): 234-240.
[23] 王雪, 杨添淞, 孙忠人, 等. 基于肠道菌群探讨针灸治疗神经、精神疾病的研究进展[J]. 神经损伤与功能重建, 2022(10): 602-603.
[24] 郭小轩, 王珑, 邹伟, 等. 基于肠道菌群理论针灸抗抑郁机制研究进展[J]. 上海针灸杂志, 2020, 39(11): 1473-1478.
[25] Obrenovich, M.E.M. (2018) Leaky Gut, Leaky Brain? Microorganisms, 6, Article No. 107. [Google Scholar] [CrossRef] 
[26] Cani, P.D., Amar, J., Iglesias, M.A., Poggi, M., Knauf, C., Bastelica, D., et al. (2007) Metabolic Endotoxemia Initiates Obesity and Insulin Resistance. Diabetes, 56, 1761-1772. [Google Scholar] [CrossRef] 
[27] Dantzer, R., O’Connor, J.C., Freund, G.G., Johnson, R.W. and Kelley, K.W. (2008) From Inflammation to Sickness and Depression: When the Immune System Subjugates the Brain. Nature Reviews Neuroscience, 9, 46-56. [Google Scholar] [CrossRef] 
[28] Köhler, C.A., Freitas, T.H., Maes, M., de Andrade, N.Q., Liu, C.S., Fernandes, B.S., et al. (2017) Peripheral Cytokine and Chemokine Alterations in Depression: A Meta‐Analysis of 82 Studies. Acta Psychiatrica Scandinavica, 135, 373-387. [Google Scholar] [CrossRef] 
[29] Capuron, L. and Miller, A.H. (2011) Immune System to Brain Signaling: Neuropsychopharmacological Implications. Pharmacology & Therapeutics, 130, 226-238. [Google Scholar] [CrossRef] 
[30] Bonaz, B., Bazin, T. and Pellissier, S. (2018) The Vagus Nerve at the In-terface of the Microbiota-Gut-Brain Axis. Frontiers in Neuroscience, 12, Article No. 49. [Google Scholar] [CrossRef] 
[31] Schmaal, L., Veltman, D.J., van Erp, T.G.M., Sämann, P.G., Frodl, T., Jahanshad, N., et al. (2015) Subcortical Brain Alterations in Major Depressive Disorder: Findings from the ENIGMA Major Depressive Disorder Working Group. Molecular Psychiatry, 21, 806-812. [Google Scholar] [CrossRef] 
[32] Kaiser, R.H., Andrews-Hanna, J.R., Wager, T.D. and Pizzagalli, D.A. (2015) A Systematic Review and Meta-Analysis of Resting-State Functional Connectivity in Major Depression. Psychological Medicine, 45, 2247-2255.
[33] de Oliveira Rodrigues, D.M., Menezes, P.R., Machado Ribeiro Si-lotto, A.E., Heps, A., Pereira Sanches, N.M., Schveitzer, M.C., et al. (2023) Efficacy and Safety of Auricular Acupuncture for Depres-sion: A Randomized Clinical Trial. JAMA Network Open, 6, e2345138. [Google Scholar] [CrossRef] 
[34] 张晓峰, 王晓莉, 李晓敏. 基于“脑肠轴”理论探讨针灸治疗帕金森病抑郁的概述[J]. 世界中西医结合杂志, 2023, 18(7): 1245-1249.
[35] Zhu, J., Chen, L., Zhao, Y., et al. (2021) Electroacupuncture at ST36 Alleviates Depressive-Like Behaviors in CUMS Rats: A Gut-Brain Axis Perspective. Brain Research Bulletin, 177, 101-111.
[36] Wang, L., Zhou, J., Li, Z., et al. (2017) Electroacu-puncture at ST36 Ameliorates Intestinal Barrier Injury and Reduces Endotoxemia in Polymicrobial Sepsis. The American Journal of Chinese Medicine, 45, 785-802.
[37] Wu, X., Tu, M., Yu, Z., Cao, Z., Qu, S., Chen, N., et al. (2024) The Efficacy and Cerebral Mechanism of Intradermal Acupuncture for Major Depressive Disorder: A Multicenter Randomized Controlled Trial. Neuropsycho-pharmacology, 50, 1075-1083. [Google Scholar] [CrossRef] 
[38] David, L.A., Maurice, C.F., Carmody, R.N., Gootenberg, D.B., Button, J.E., Wolfe, B.E., et al. (2013) Diet Rapidly and Reproducibly Alters the Human Gut Microbiome. Nature, 505, 559-563. [Google Scholar] [CrossRef] 
[39] Costea, P.I., Zeller, G., Sunagawa, S., Pelletier, E., Alberti, A., Levenez, F., et al. (2017) Towards Standards for Human Fecal Sample Processing in Metagenomic Studies. Nature Biotechnology, 35, 1069-1076. [Google Scholar] [CrossRef] 
[40] Zhang, L., Wang, X., Wang, W., et al. (2019) Electroacupuncture Ameliorates Chronic Unpredictable Mild Stress-Induced Depressive-Like and Anxiety-Like Behavior by Suppressing NLRP3 Inflammasome in Hippocam-pus. Neuroscience Letters, 711, Article ID: 134421.
[41] Sun, J., Shao, Y., Liu, Y., et al. (2020) Electroacupuncture Ameliorates De-pressive-Like Behaviors by Inhibiting NLRP3 Inflammasome Activation in the Hippocampus of Rats. Brain Research Bulletin, 162, 70-78.
[42] Jia, Y., Wang, W., Liu, Z., et al. (2017) Electroacupuncture Improves Depression-Like Behavior in Rats by Promoting Adult Hippocampal Neurogenesis. Scientific Reports, 7, Article No. 45032.
[43] Liang, J., Yin, C., He, Y., et al. (2021) Electroacu-puncture Ameliorates Depressive-Like Behaviors by Regulating the Kynurenine Metabolism Pathway in the Hippocampus and Colon. Brain, Behavior, and Immunity, 94, 258-268.
[44] Cenit, M.C., Nuevo, I.C., Codoñer-Franch, P., Dinan, T.G. and Sanz, Y. (2017) Gut Microbiota and Attention Deficit Hyperactivity Disorder: New Perspectives for a Challenging Condition. European Child & Ado-lescent Psychiatry, 26, 1081-1092. [Google Scholar] [CrossRef] 
[45] Zhou, H., Zhong, H., Ying, W., Li, Z., Nie, Y. and Zhang, B. (2025) Acupuncture for the Anxiety and Depression in Parkinson Disease: A Systematic Review and Network Me-ta-Analysis. Medicine, 104, e42136. [Google Scholar] [CrossRef] 
[46] Li, Y., Zheng, H. and Stener-Victorin, E. (2020) Acupuncture for Functional Hypothalamic Amenorrhea: A Systematic Review and Meta-Analysis. Complementary Therapies in Medicine, 48, Article ID: 102272.
[47] Li, X.Y., Liu, Y.P., Wang, J., et al. (2015) A Systematic Review and Meta-Analysis of the Effects of Electroacupuncture on the Rat Model of Depression. Scientific Reports, 5, 1-10.
[48] 王婧, 赵晓峰, 郝婷, 等. 抑郁症与微生物-肠-脑轴的关系及中医药防治研究进展[J]. 人民军医, 2020, 63(6): 613-617.
[49] 汤明杰, 杨洁, 孙永, 等. 基于肠道菌群学说的中医药治疗抑郁症研究进展[J]. 中国中医药现代远程教育, 2023(16): 196-199.
[50] Han, J. (2003) Acupuncture: Neuropeptide Release Produced by Electrical Stimulation of Different Frequencies. Trends in Neurosciences, 26, 17-22. [Google Scholar] [CrossRef] 
[51] Zhang, R., Lao, L., Ren, K. and Berman, B.M. (2014) Mechanisms of Ac-upuncture-Electroacupuncture on Persistent Pain. Anesthesiology, 120, 482-503. [Google Scholar] [CrossRef] 
[52] Dhond, R.P., Kettner, N. and Napadow, V. (2007) Neuroimaging Acupunc-ture Effects in the Human Brain. The Journal of Alternative and Complementary Medicine, 13, 603-616. [Google Scholar] [CrossRef] 
[53] World Health Organization (2017) Depression and Other Common Mental Disorders: Global Health Estimates. World Health Organization.