基于脑-肠轴探讨针灸治疗缺血性卒中机制的基础研究进展

doi:10.3969/j.issn.1673-5765.2025.04.013

摘要/Abstract

摘要： 针灸作为传统医学的重要组成部分，近年来在缺血性卒中治疗中的机制受到广泛关注。本文对针灸通过干预脑-肠轴治疗缺血性卒中的相关基础研究进行汇总分析，发现其可能涉及以下机制：其一，调节肠道菌群组成，抑制致病菌增殖并促进有益菌定植，同时增强肠上皮紧密连接蛋白表达以维持肠道屏障功能，减少肠源性毒素入血；其二，通过神经内分泌调控抑制下丘脑-垂体-肾上腺轴过度激活，降低促炎因子释放，并激活迷走神经介导的抗炎通路；其三，调节短链脂肪酸、氧化三甲胺等肠道菌群代谢产物的动态平衡，改善全身炎症微环境；其四，重塑免疫细胞亚群比例，抑制过度炎症反应并促进神经修复。本文通过梳理近年来的研究成果，探讨针灸通过脑-肠轴调控缺血性卒中的靶点与潜在通路，为后续相关基础研究及针灸的临床应用提供依据。

文章导读： 针灸作为传统医学的一项重要疗法，通过调节脑-肠轴在缺血性卒中治疗中展现出独特潜力。尽管现有研究已初步揭示了针灸通过脑-肠轴治疗卒中的可能机制，但其具体分子机制及关键靶点仍需进一步探索。

关键词: 针灸; 缺血性卒中; 脑-肠轴; 肠道菌群; 肠道屏障; 免疫调节

Abstract: Acupuncture, as an important part of traditional Chinese medicine, has received widespread attention in recent years for its mechanisms in the treatment of ischemic stroke. This paper summarizes and analyzes the basic research on acupuncture treating ischemic stroke through modulation of the gut-brain axis. It is found that it may involve the following mechanisms. Firstly, it modulates the gut microbiota composition by inhibiting the proliferation of pathogenic bacteria and promoting the colonization of beneficial bacteria. It also enhances the expression of intestinal epithelial tight junction protein to maintain gut barrier function and reduce enterotoxin entry into the bloodstream. Secondly, it inhibits the overactivation of the hypothalamic-pituitary-adrenal axis through neuroendocrine regulation, reduces the release of pro-inflammatory cytokine, and activates the anti-inflammatory pathways mediated by the vagus nerve. Thirdly, it regulates the dynamic balance of gut microbiota metabolic products such as short-chain fatty acids and trimethylamine N-oxide, ameliorating the systemic inflammatory microenvironments. Fourthly, it reshapes the proportion of immune cell subpopulations, inhibits excessive inflammation reactions, and facilitates neural repair. By synthesizing recent research advancements, this paper reviews potential therapeutic targets and pathways through which acupuncture modulates ischemic stroke via the gut-brain axis, aiming to provide a basis for subsequent basic research and clinical application of acupuncture.

Key words: Acupuncture; Ischemic stroke; Gut-brain axis; Gut microbiota; Gut barrier; Immune regulation

中图分类号:

R74
R245

赵乾坤, 李宪东, 徐天策, 陈会生. 基于脑-肠轴探讨针灸治疗缺血性卒中机制的基础研究进展[J]. 中国卒中杂志, 2025, 20(4): 486-492.

ZHAO Qiankun, LI Xiandong, XU Tiance, CHEN Huisheng. Research Progress on the Mechanism of Acupuncture in Treating Ischemic Stroke Based on the Gut-Brain Axis[J]. Chinese Journal of Stroke, 2025, 20(4): 486-492.

参考文献

[1] LI X Y，KONG X M，YANG C H，et al. Global，regional，and national burden of ischemic stroke，1990—2021：an analysis of data from the global burden of disease study 2021[J/OL]. EClinicalMedicine，2024，75：102758[2024-06-10]. https://doi.org/10.1016/j.eclinm.2024.102758.
[2] 王拥军，熊云云，李光硕，等. 卒中：回眸2023[J]. 中国卒中杂志，2024，19（1）：1-21.
WANG Y J，XIONG Y Y，LI G S，et al. Highlights in stroke in 2023[J]. Chin J Stroke，2024，19（1）：1-21.
[3] 黄卫，吴海波，冯伦冬，等. 针刺联合康复治疗对老年脑卒中患者免疫功能和神经功能的影响[J]. 针刺研究，2018，43（9）：567-572.
HUANG W，WU H B，FENG L D，et al. Effect of acupuncture combined with rehabilitation on immune and neural functions in elderly patients with stroke[J]. Acupuncture Research，2018，43（9）：567-572.
[4] 赵丽莉，吴林纳，孙一鸣，等. 基于肠道菌群探讨针灸治疗缺血性脑卒中的研究进展[J]. 现代中西医结合杂志，2024，33（4）：572-576，584.
ZHAO L L，WU L N，SUN Y M，et al. Research progress on acupuncture treatment for ischemic stroke based on gut microbiota[J]. Modern Journal of Integrated Traditional Chinese and Western Medicine，2024，33（4）：572-576，584.
[5] CRYAN J F，O’RIORDAN K J，COWAN C S M，et al. The microbiota-gut-brain axis[J]. Physiol Rev，2019，99（4）：1877-2013.
[6] CUI W，XU L，HUANG L，et al. Changes of gut microbiota in patients at different phases of stroke[J]. CNS Neurosci Ther，2023，29（11）：3416-3429.
[7] LU L，ZHANG X G，ZHONG L L，et al. Acupuncture for neurogenesis in experimental ischemic stroke：a systematic review and meta-analysis[J/OL]. Sci Rep，2016，6：19521[2024-06-10]. https://doi.org/10.1038/srep19521.
[8] CHAVEZ L M，HUANG S S，MACDONALD I，et al. Mechanisms of acupuncture therapy in ischemic stroke rehabilitation：a literature review of basic studies[J/OL]. Int J Mol Sci，2017，18（11）：2270[2024-06-10]. https://doi.org/10.3390/ijms18112270.
[9] HANSCOM M，LOANE D J，SHEA-DONOHUE T. Brain-gut axis dysfunction in the pathogenesis of traumatic brain injury[J/OL]. J Clin Invest，2021，131（12）：e143777[2024-06-10]. https://doi.org/10.1172/JCI143777.
[10] DE PUNDER K，PRUIMBOOM L. Stress induces endotoxemia and low-grade inflammation by increasing barrier permeability[J/OL]. Front Immunol，2015，6：223[2024-06-10]. https://doi.org/10.3389/fimmu.2015.00223.
[11] AGIRMAN G，HSIAO E Y. SnapShot：the microbiota-gut-brain axis[J]. Cell，2021，184（9）：2524-2524.
[12] BENAKIS C，BREA D，CABALLERO S，et al. Commensal microbiota affects ischemic stroke outcome by regulating intestinal γδ T cells[J]. Nat Med，2016，22（5）：516-523.
[13] LEE J，D’AIGLE J，ATADJA L，et al. Gut microbiota-derived short-chain fatty acids promote poststroke recovery in aged mice[J]. Circ Res，2020，127（4）：453-465.
[14] DOIFODE T，GIRIDHARAN V V，GENEROSO J S，et al. The impact of the microbiota-gut-brain axis on Alzheimer’s disease pathophysiology[J/OL]. Pharmacol Res，2021，164：105314[2024-06-10]. https://doi.org/10.1016/j.phrs.2020.105314.
[15] SORBONI S G，MOGHADDAM H S，JAFARZADEH-ESFEHANI R，et al. A comprehensive review on the role of the gut microbiome in human neurological disorders[J/OL]. Clin Microbiol Rev，2022，35（1）：e0033820[2024-06-10]. https://doi.org/10.1128/CMR.00338-20.
[16] SHICHITA T，SUGIYAMA Y，OOBOSHI H，et al. Pivotal role of cerebral interleukin-17-producing gammadelta T cells in the delayed phase of ischemic brain injury[J]. Nat Med，2009，15（8）：946-950.
[17] WEN X，DONG H，ZOU W. The role of gut microorganisms and metabolites in intracerebral hemorrhagic stroke：a comprehensive review[J/OL]. Front Neurosci，2024，18：1346184[2024-06-10]. https://doi.org/10.3389/fnins.2024.1346184.
[18] DALILE B，VAN OUDENHOVE L，VERVLIET B，et al. The role of short-chain fatty acids in microbiota-gut-brain communication[J]. Nat Rev Gastroenterol Hepatol，2019，16（8）：461-478.
[19] MURTHY P M，CA J，KANDI V，et al. Connecting the dots：the interplay between stroke and the gut-brain axis[J/OL]. Cureus，2023，15（4）：e37324[2024-06-10]. https://doi.org/10.7759/cureus.37324.
[20] WANG M，LIU W L，GE J Y，et al. The immunomodulatory mechanisms for acupuncture practice[J/OL]. Front Immunol，2023，14：1147718[2024-06-10]. https://doi.org/10.3389/fimmu.2023.1147718.
[21] HAN S N，CAI L H，CHEN P P，et al. A study of the correlation between stroke and gut microbiota over the last 20 years：a bibliometric analysis[J/OL]. Front Microbiol，2023，14：1191758[2024-06-10]. https://doi.org/10.3389/fmicb.2023.1191758.
[22] CUI J W，SONG W R，JIN Y P，et al. Research progress on the mechanism of the acupuncture regulating neuro-endocrine-immune network system[J/OL]. Vet Sci，2021，8（8）：149[2024-06-10]. https://doi.org/10.3390/vetsci8080149.
[23] XIAN M H，SHEN L，ZHAN S K，et al. Integrated 16S rRNA gene sequencing and LC/MS-based metabolomics ascertained synergistic influences of the combination of acupuncture and NaoMaiTong on ischemic stroke[J/OL]. J Ethnopharmacol，2022，293：115281[2024-06-10]. https://doi.org/10.1016/j.jep.2022.115281.
[24] CAI W，WEI X F，ZHANG J R，et al. Acupuncture ameliorates depression-like behavior of poststroke depression model rats through the regulation of gut microbiota and NLRP3 inflammasome in the colon[J]. Neuroreport，2024，35（14）：883-894.
[25] 崔振华，林夏妃，陈永敏，等. 针灸与康复疗法干预脑缺血模型大鼠神经功能及肠道菌群的变化[J]. 中国组织工程研究，2023，27（17）：2692-2698.
CUI Z H，LIN X F，CHEN Y M，et al. Acupuncture and moxibustion combined with rehabilitation therapy improve neurological function and intestinal flora following cerebral ischemia in rats[J]. Chinese Journal of Tissue Engineering Research，2023，27（17）：2692-2698.
[26] CHELAKKOT C，GHIM J，RYU S H. Mechanisms regulating intestinal barrier integrity and its pathological implications[J]. Exp Mol Med，2018，50（8）：1-9.
[27] ZHENG Y D，BONFILI L，WEI T，et al. Understanding the gut-brain axis and its therapeutic implications for neurodegenerative disorders[J/OL]. Nutrients，2023，15（21）：4631[2024-06-10]. https://doi.org/10.3390/nu15214631.
[28] JONES M P，DILLEY J B，DROSSMAN D，et al. Brain-gut connections in functional GI disorders：anatomic and physiologic relationships[J]. Neurogastroenterol Motil，2006，18（2）：91-103.
[29] YANG N N，YANG J W，YE Y，et al. Electroacupuncture ameliorates intestinal inflammation by activating α7nAChR-mediated JAK2/STAT3 signaling pathway in postoperative ileus[J]. Theranostics，2021，11（9）：4078-4089.
[30] ZHU J，WANG C，WANG Y，et al. Electroacupuncture alleviates anxiety and modulates amygdala
CRH/CRHR1 signaling in single prolonged stress mice[J]. Acupunct Med，2022，40（4）：369-378.
[31] ZHENG J Y，WANG Y，ZHANG C，et al. Electroacupuncture negatively regulates the Nesfatin-1/ERK/CREB pathway to alleviate HPA axis hyperactivity and anxiety-like behaviors caused by surgical trauma[J/OL]. Chin Med，2024，19（1）：108[2024-06-10]. https://doi.org/10.1186/s13020-024-00974-2.
[32] 马伊笛，孙晓伟，运锋. 穴位电刺激对卒中后抑郁大鼠行为学及神经递质水平影响[J]. 针灸临床杂志，2022，38（11）：44-50.
MA Y D，SUN X W，YUN F. Effects of acupoints electric stimulation on behavior and neurotransmitters in rats with post-stroke depression[J]. JCAM，2022，38（11）：44-50.
[33] 韩名媛，高睿泽，杨成妍，等. 针刺治疗卒中后抑郁的神经–内分泌–免疫网络机制[J]. 中国针灸，2024，44（9）：1100-1106.
HAN M Y，GAO R Z，YANG C Y，et al. Neuro-endocrine-immune network mechanism of acupuncture for post-stroke depression[J]. Chinese Acupuncture & Moxibustion，2024，44（9）：1100-1106.
[34] CHIDAMBARAM S B，RATHIPRIYA A G，MAHALAKSHMI A M，et al. The influence of gut dysbiosis in the pathogenesis and management of ischemic stroke[J/OL]. Cells，2022，11（7）：1239[2024-06-10]. https://doi.org/10.3390/cells11071239.
[35] PEH A，O’DONNELL J A，BROUGHTON B R S，et al. Gut microbiota and their metabolites in stroke：a
double-edged sword[J]. Stroke，2022，53（5）：1788-1801.
[36] MIRZAEI R，BOUZARI B，HOSSEINI-FARD S R，et al. Role of microbiota-derived short-chain fatty acids in nervous system disorders[J/OL]. Biomed Pharmacother，2021，139：111661[2024-06-10]. https://doi.org/10.1016/j.biopha.2021.111661.
[37] ROTH W，ZADEH K，VEKARIYA R，et al. Tryptophan metabolism and gut-brain homeostasis[J/OL].
Int J Mol Sci，2021，22（6）：2973[2024-06-10]. https://doi.org/10.3390/ijms22062973.
[38] LI S，ZHAO X Y，LIN F H，et al. Gut flora mediates the rapid tolerance of electroacupuncture on ischemic stroke by activating melatonin receptor through regulating indole-3-propionic acid[J]. Am J Chin Med，2022，50（4）：979-1006.
[39] 张忠平，张海月. 针刺调节缺血性中风大鼠肠道中短链脂肪酸、氧化三甲胺的研究[J]. 中国民间疗法，2022，30（3）：87-89.
ZHANG Z P，ZHANG H Y. Effects of acupuncture on short-chain fatty acids and trimethylamine N-oxide in rats with ischemic stroke[J]. China’s Naturopathy，2022，30（3）：87-89.
[40] KE X H，XIANG Q，JIANG P L，et al. Effect of electroacupuncture on short-chain fatty acids in peripheral blood after middle cerebral artery occlusion/reperfusion in rats based on gas chromatography-mass spectrometry[J/OL]. Mediators Inflamm，2022，2022：3997947[2024-06-10]. https://doi.org/10.1155/2022/3997947.
[41] LIU S，MEN X J，GUO Y，et al. Gut microbes exacerbate systemic inflammation and behavior disorders in neurologic disease CADASIL[J/OL]. Microbiome，2023，11（1）：202[2024-06-10]. https://doi.org/10.1186/s40168-023-01638-3.
[42] ZHANG F，DENG Y T，WANG H D，et al. Gut microbiota-mediated ursodeoxycholic acids regulate the inflammation of microglia through TGR5 signaling after MCAO[J/OL]. Brain Behav Immun，2024，115：667-679[2024-06-10]. https://doi.org/10.1016/j.bbi.2023.11.021.
[43] ZHANG Q Q，DENG P Y，CHEN S H，et al. Electroacupuncture and human iPSC-derived small extracellular vesicles regulate the gut microbiota in ischemic stroke via the brain-gut axis[J/OL]. Front Immunol，2023，14：1107559[2024-06-10]. https://doi.org/10.3389/fimmu.2023.1107559.
[44] CAI W，MA W，WANG G T，et al. Antidepressant，anti-inflammatory，and antioxidant effects of electroacupuncture through sonic hedgehog-signaling pathway in a rat model of poststroke depression[J/OL]. Neuropsychiatr Dis Treat，2019，15：1403-1411[2024-06-10]. https://doi.org/10.2147/NDT.S205033.