nav emailalert searchbtn searchbox tablepage yinyongbenwen piczone journalimg journalInfo journalinfonormal searchdiv searchzone qikanlogo popupnotification paper paperNew
中药单体、活性成分、中药复方及中医通过神经-内分泌-免疫系统治疗失眠的作用机制与临床研究进展
基金项目(Foundation): 中央引导地方科技发展专项(编号:2025ZY036/YDZX 20206200002673); 甘肃省名中医传承工作室建设项目(批复文号:甘卫中医函[2023] 62号); 甘肃省科技计划项(编号:24YANA007/23YFFA0027/24CXKA009); 高校产业支撑计划项目(编号:2024CYZC-40/2020C-09); 甘肃省中医药科研课题(编号:GZKG-2024-47)
邮箱(Email): 572551201@qq.com
DOI: 10.13412/j.cnki.zyyl.20260630.002
发布时间: 2026-06-30
出版时间: 2026-06-30
网络发布时间: 2026-06-30
移动端阅读
摘要:

失眠作为复杂的生理病理综合征,其发生发展与神经-内分泌-免疫(neuroendocrine-immune,NEI)系统稳态失衡存在密切关联。本文从NEI系统调控视角,系统梳理了中医药(含中药单体、复方及针刺疗法)干预失眠的作用机制与临床研究进展。现代药理研究证实,中药活性成分通过精准作用于调节神经递质、抑制HPA轴亢进、调控炎症因子等关键节点发挥效应,经典复方则体现多靶点协同调控特征,而针刺治疗通过选取百会、神门、三阴交等穴位,可同步调节NEI系统中神经递质、内分泌激素及免疫因子水平,优化睡眠结构。现有研究表明,中医药通过整体调控模式作用于NEI系统,充分契合中医“辨证论治”的核心优势。未来研究需进一步明确中药作用的受体与信号机制,并推动建立中医药治疗失眠的现代化评价体系与规范化临床方案。

Abstract:

Insomnia, as a complex physiological and pathological syndrome, is closely associated with homeostatic imbalance of the neuroendocrine-immune (NEI) system. This paper systematically reviews the mechanism and clinical research progress of traditional Chinese medicine (TCM) interventions (including monomers, compounds, and acupuncture) in treating insomnia from the perspective of NEI system regulation. Modern pharmacological studies have demonstrated that TCM active components exert effects by precisely targeting key nodes, such as modulating neurotransmitters, inhibiting hypothalamic-pituitary-adrenal (HPA) axis hyperactivity, and regulating inflammatory factors. Classical compounds synergistically regulate multiple targets. Additionally, acupuncture therapy simultaneously regulates neurotransmitter, endocrine hormone, and immune factor levels in the NEI system by selecting acupoints such as Baihui (百会, GV20), Shenmen (神门, HT7), and Sanyinjiao (三阴交, SP6), thereby optimizing sleep architecture. Existing research indicates that TCM exerts holistic regulatory effects on the NEI system, fully aligning with the core advantage of TCM’s “syndrome differentiation and treatment”. Future studies should further elucidate the receptors and signaling mechanisms underlying TCM effects and promote the establishment of modern evaluation systems and standardized clinical protocols for TCM-based insomnia treatment.

参考文献

[1] Zhong Y,Zheng Q,Hu P Y,et al. Sedative and hypnotic effects of inhalation of compound Anshen essential oil and GC-MS analysis of chemical constituents[J]. Nat Prod Res Dev,2019,31:1528-1536.

[2] Morin C M,Jarrin D C. Epidemiology of insomnia:prevalence,course,risk factors,and public health burden[J]. Sleep medicine clinics,2022,17(2):173-191.

[3] 中国睡眠研究会,等. 2025中国健康睡眠研究白皮书 [R/OL]. 北京:中国睡眠研究会,2025 [2025-12-10].

[4] 中国中西医学会失眠障碍中西医结合诊疗专家共识项目组.失眠障碍中西医结合诊疗专家共识[J].中国新药杂志,2026,35(6):597-608.

[5] CHAKRAVORTY S,PILLAI M. Sleepless and Vulnerable:The Hidden Dangers of Insomnia in Opioid Addiction [J]. Sleep,2025,48(4):zsae315.

[6] 王冠英,袁香梅,刘涛,等.中医不寐五神分型病机与辨治[J].中华中医药杂志,2025,40(2):590-594.

[7] 谈钰濛,杨思红,向兴华,等. 以温阳补肾法论治失眠[J]. 中国中医基础医学杂志,2024,30(9):1603-1605.

[8] Basedovsky H. Network of immuneneuroendocrine interactions[J]. Clin Exp Imunol,1977,27:1-12.

[9] Cui J,Song W,Jin Y,et al. Research progress on the mechanism of the acupuncture regulating neuro-endocrine-immune network system[J]. Veterinary sciences,2021,8(8):149.

[10] 闫冰,蒋海琳,马天姝,等.针刺治疗失眠的神经-内分泌-免疫系统机制[J].时珍国医国药,2021,32(7):1696-1698.

[11] Abelaira H M,Réus G Z,Petronilho F,et al. Neuroimmunomodulation in depression:a review of inflammatory cytokines involved in this process[J]. Neurochemical research,2014,39(9):1634-1639.

[12] Spangelo B L,Gorospe W C. Role of the cytokines in the neuroendocrine-immune system axis[J]. Frontiers in Neuroendocrinology,1995,16(1):1-22.

[13] 张飞燕,李晶晶,周莹,等. 安神类中药及其有效成分对神经递质镇静催眠机制的研究进展 [J]. 中国中药杂志,2016,41(23):4320-4327.

[14] 王子涵,张杰,刘飞祥,等.中药调节脑神经递质治疗失眠研究进展[J/OL].中国实验方剂学杂志,1-14[2025-09-16].

[15] HEPSOMALI P,GROEGER J A,NISHIHIRA J,et al. Effects of Oral Gamma-Aminobutyric Acid (GABA) Administration on Stress and Sleep in Humans:A Systematic Review [J]. Front Neurosci,2020,14:923.

[16] Strekalova,T.; Evans,M.; Chernopiatko,A.; Couch,Y.; Costa-Nunes,J.; Cespuglio,R.; Chesson,L.; Vignisse,J.; Steinbusch,H.W.; Anthony,D.C.; et al. Deuterium content of water increases depression susceptibility:The potential role of a serotonin-related mechanism. Behav[J]. Brain Res,2015,277,237–244.

[17] Si,L.; Wang,Y.; Wuyun,G.; Bao,L.; Agula,B. The effect of Mongolian medical acupuncture on cytokines and neurotransmitters in the brain tissue of insomniac rats. Eur. J. Integr[J]. Med, 2015, 7,492–498.

[18] 范琳琳,于莉,陈智慧.中西医治疗不寐的机制及临床研究进展[J/OL].实用中医内科杂志,1-9[2025-09-22].

[19] Xia L,Chen G H,Li Z H,et al. Alterations in hypothalamus-pituitary-adrenal/thyroid axes and gonadotropin-releasing hormone in the patients with primary insomnia:a clinical research[J]. PloS one,2013,8(8):e71065.

[20] Choi K,Lee Y J,Park S,et al. Efficacy of melatonin for chronic insomnia:Systematic reviews and meta-analyses[J]. Sleep medicine reviews,2022,66:101692.

[21] Li C,Huang B,Zhang Y W. Chinese herbal medicine for the treatment of depression:effects on the neuroendocrine-immune network[J]. Pharmaceuticals,2021,14(1):65.

[22] Hou Z,Chen Y,Sun Y,et al.Sleep duration and insomnia with comorbid depression and anxiety symptoms in Chinese adults:a cross-sectional study[J].Nat Sci Sleep,2023,15:1079-1091.

[23] 张志兰,张文跃,宋义勇,等.伴失眠的抑郁症患者认知功能及血清炎性细胞因子水平研究[J].临床精神医学杂志,2020,30(6):401-403.

[24] Krueger J M. The role of cytokines in sleep regulation[J]. Current pharmaceutical design,2008,14(32):3408-3416.

[25] GAILLARD R C. Neuroendocrine-immune system interactions: the immune-hypothalamo-pituitary-adrenal axis[J]. Trends in Endocrinology & Metabolism, 1994, 5(7): 303-309.

[26] Ahmad S B,Ali A,Bilal M,et al. Melatonin and health:insights of melatonin action,biological functions,and associated disorders[J]. Cellular and molecular neurobiology,2023,43(6):2437-2458.

[27] Broderick M Z L,Khan Q,Moradikor N. Understanding the connection between stress and sleep:From underlying mechanisms to therapeutic solutions[J]. Progress in Brain Research,2025,291:137-159.

[28] CAO J X,ZHANG Q,ZHAO Y Y.Hypnotic effect of jujubosides from Semen Ziziphi Spinosae[J].J Ethnopharmacol,2010,130(1):163.

[29] 丁灵,王欣,上官惠子,等.酸枣仁的化学成分及治疗失眠的作用机制研究进展[J].现代中医药,2025,45(3):14-23.

[30] 吴垚,王佳伟,马叶子,等.远志化学成分及药理作用研究进展[J].陕西中医药大学学报,2025,48(1):5-14.

[31] WANG L E,CUI X Y,CUI S Y,et al. Potentiating effect of spinosin,a C-glycoside flavonoid of Semen Ziziphi spinosae,on pentobarbital-induced sleep may be related to postsynaptic 5-HT1A receptors [J]. Phytomedicine,2010,17(6):404-409.

[32] ZHONG Y H,JIANG S,QU W M,et al. Saikosaponin a promotes sleep by decreasing neuronal activities in the lateral hypothalamus[J].J Sleep Res,2022,31(2):e13484.

[33] 孙宾,郝洪谦,郑开俊,等.柴胡皂甙调节猫睡眠节律电活动机理的初探[J].天津医科大学学报,2000,6(3):274-276.

[34] Bai Z J,Gao T T,Zhang R,et al. Inhibition of IL-6methylation by saikosaponin C regulates neuroinflammation to alleviate depression[J]. Int Immunopharmacol,2023,118:110043.

[35] SU J,PAN Y W,WANG S Q,et al.Saikosaponin-d attenuated lipopolysaccharide-induced depressive-like behaviors via inhibiting microglia activation and neuroinflammation[J].Int Immunopharmacol,2020,80:106181.

[36] LI J Y,ZHANG Y,WANG S,et al. Ginsenoside Rg1 alleviates PCPA-induced insomnia by inhibiting NLRP3 inflammasome activation and pyroptosis through the Nrf2/HO-1 pathway in mice[J]. Psychopharmacology,2025:1-17.

[37] Herlenius E, Lagercrantz H. Development of neurotransmitter systems during critical periods[J]. Experimental neurology, 2004, 190: 8-21.

[38] KIM J W,KIM C S,HU Z,et al. Enhancement of pentobarbital-induced sleep by apigenin through chloride ion channel activation [J]. Arch Pharm Res,2012,35(2):367-373.

[39] LOSI G,PUIA G,GARZON G,et al. Apigenin modulates GABAergic and glutamatergic transmission in cultured cortical neurons [J]. Eur J Pharmacol,2004,502(1):41-46.

[40] 胡金颖,代立霞,张丹参,等.酸枣仁中黄酮类物质药理作用研究进展[J].中国药理学与毒理学杂志,2021,35(10):785-786.

[41] HAO K-X,SHEN C-Y,JIANG J-G. Sedative and hypnotic effects of Polygala tenuifolia willd. saponins on insomnia mice and their targets [J]. J Ethnopharmacol,2024,323:117618.

[42] 王文通.菊花提取物镇静催眠作用研究[D].河南大学,2020.

[43] Yang WS,Kim D,Yi YS,et al. AKT-targeted anti-inflammatory activity of the methanol extract of Chrysanthemum indicum var. albescens[J]. Journal of ethnopharmacology,2017,201:82-90.

[44] 李佳璇.基于系统药理学探讨四味安睡饮治疗昼夜节律失调性睡眠觉醒障碍的作用机制[D].青岛:青岛大学,2023.

[45] Zielinski M R,Gibbons A J. Neuroinflammation,sleep,and circadian rhythms[J]. Front Cell Infect Microbiol,2022,12:853096.

[46] Guo R,Li L,Su J,et al. Pharmacological activity and mechanism of tanshinone IIA in related diseases[J]. Drug Design,Development and Therapy,2020:4735-4748.

[47] Cao W,Guo X,Zheng H,et al. Current progress of research on pharmacologic actions of salvianolic acid B[J]. Chinese journal of integrative medicine,2012,18(4):316-320.

[48] 王婷婷,王芮,杨伟丽,等.六味安神中药对小鼠镇静催眠作用影响的研究[J].河北中医药学报,2021,36(2):1-5.

[49] 王玉,杨雪,夏鹏飞,等.酸枣仁汤化学成分、药理作用、临床应用的研究进展及质量标志物的预测分析[J].中国中药杂志,2020,45(12):2765-2771.

[50] 郭帆,吴东南,刘玲,等.酸枣仁汤防治睡眠剥夺性大鼠学习记忆功能变化及其对NLRP3通路的影响[J].中国实验方剂学杂志,2021,27(2):22-27.

[51] 黄小圆,郝志成,杜帅霖,等.酸枣仁汤对抑郁模型大鼠细胞外信号调节激酶-核因子通路的影响[J].世界中医药,2025,20(16):2864-2869+2877.

[52] 吴东南,丁瑞丛,纪可,等.酸枣仁汤对慢性睡眠剥夺大鼠学习记忆及TLR4/NF-κB信号通路的影响[J].中国实验方剂学杂志,2020,26(6):18-24.

[53] 郭杰,尹晓刚.酸枣仁汤对老年失眠模型大鼠学习记忆能力及脑内神经递质含量的影响[J].中国药房,2016,27(22):3085-3087.

[54] 章新友,王姝,唐琍萍,等.酸枣仁汤治疗失眠及作用机制研究进展[J].中华中医药学刊,2022,40(10):1-7.

[55] 胡霖霖,刘文娟,张蕾,等.加味酸枣仁汤对焦虑性失眠患者躯体过度觉醒水平的影响[J].浙江临床医学,2020,22(8):1123-1125.

[56] 张仲景.金匮要略[M].北京:中医古籍出版社,1997:8.

[57] XUE X Y,ZHANG H X,PAN J,et al. The role for GABAergic interneurons subtypes in the antidepressant efficacy of traditional Chinese medicine formula Lily Bulb and Rehmannia Decoction[J]. Chinese Journal of Experimental Traditional Medical Formulae,2021,27(22): 1-8.

[58] 胡超,赵洪庆,刘检,等.基于谱效关系及活性验证的百合地黄汤抗抑郁成分研究[J].药学学报,2024,59(5):1364-1373.

[59] 郑竹宏.百合地黄汤治疗失眠的作用机制研究[D].北京:北京中医药大学,2019.

[60] 管家齐,孙燕,陈海伟.百合地黄汤对小鼠抑郁症模型的影响[J].中华中医药杂志,2013,28(6):1875-1877.

[61] 胡兆东.鲜百合(冻干)饮片制备及养阴润肺、清心安神药效研究[D].郑州:河南中医药大学,2022.

[62] 余湘浩,何华,王晓雯.百合地黄汤治疗失眠伴抑郁焦虑的药理机制与临床应用研究进展[J].湖南中医药大学学报,2024,44(6):1133-1139.

[63] 赵洪庆,唐林,吴碧茹,等.百合地黄汤抑制NLRP3炎症小体激活改善焦虑性抑郁症模型大鼠海马神经元损伤[J].中国实验方剂学杂志,2021,27(20):7-14.

[64] 金岚.天王补心丹的传统认识与现代研究[J].中成药研究,1982,4(5):32-34.

[65] 杨文育,李云海,唐飞越,等.基于肠道菌群研究天王补心丹通过调控单胺代谢治疗失眠的作用及机制[J].中华中医药杂志,2025,40(3):1392-1396.

[66] 黄佳颖,李劲草,顾永芳,等.加味天王补心丹对模拟高原暴露模型大鼠睡眠的改善作用及其机制[J].中国药理学与毒理学杂志,2024,38(6):401-409.

[67] 张卓,姜杰程,黎柱江,等.天王补心丹含药血清通过调控Trpv1/AMPK通路缓解腺苷诱导的神经炎症与细胞凋亡的机制研究[J/OL].中国中药杂志,1-11[2026-01-24].

[68] 张岑炜,于峥,刘寨华,等.温胆汤在明清时期类方的衍化发展[J].中国中医基础医学杂志,2022,28(2):197-200.

[69] 李亮,王珠强,胡莹,等.基于神经递质和5-HT1A/Gαi/o/cAMP信号通路研究黄连温胆汤对失眠大鼠的治疗作用及机制[J].中药新药与临床药理,2023,34(5):591-598.

[70] 胡莹,李亮,戴卫波,等.黄连温胆汤对氯苯丙氨酸致失眠小鼠的睡眠改善及γ-氨基丁酸能系统通路递质含量及受体表达的影响[J].中药新药与临床药理,2022,33(8):1009-1016.

[71] 贾利利,周宁,李凯,等.黄连阿胶汤对对氯苯丙氨酸致失眠模型小鼠神经递质的影响[J].中国实验方剂学杂志,2012,18(22):240-242.

[72] 陈建,陈敏捷.黄连阿胶汤对失眠大鼠血清Th1/Th2平衡的影响[J].长春中医药大学学报,2014,30(5):779-781.

[73] 王宏斌,杨如意,曹昌霞,等.艾灸结合黄连阿胶汤对PCPA致失眠大鼠神经递质5-HT、5-HIAA、NE、IL-6水平的影响[J].时珍国医国药,2022,33(7):1623-1626.

[74] 杜鹃,王利平.桂枝加龙骨牡蛎汤合黄连阿胶汤加味治疗围绝经期失眠[J].实用中西医结合临床,2021,21(11):38-39.

[75] 吴金鸿,张星平,闫德祺,等.桂枝加龙骨牡蛎汤对肺不藏魄型不寐模型大鼠IL-10及TNF-α表达的影响[J].中国实验方剂学杂志,2024,30(13):20-27.

[76] 张育贵,张淑娟,牛江涛,等.四逆散镇静催眠作用研究进展及其新药开发的策略分析[J].中草药,2020,51(13):3575-3584.

[77] 李玉萍,徐瑞鑫,李廷利.四逆散冻干粉对睡眠剥夺果蝇头部5-HT含量和5-HT 1A受体表达的影响[J].中国中药杂志,2010,35(20):2749-2751.

[78] Lin C T,Lin H Y,Peng W H,et al. Multi-Target mechanisms of Si-Ni-San on anxious insomnia:an example of Network-pharmacology and molecular Docking analysis[J]. Current Medicinal Chemistry,2025,32(13):2640-2663.

[79] 叶晓楠.空瓶刺激诱导慢性情绪应激所致大鼠睡眠障碍的细胞因子机制与四逆散有效组分的干预作用研究[D].哈尔滨:黑龙江中医药大学,2016.

[80] JIAO H Y,YAN Z Y,MA Q Y,et al.Influence ofXiaoyaosan on depressive-like behaviors in chronicstress-depressed rats through regulating tryptophan metabolismin hippocampus[J].Neuropsychiatr Dis Treat,2019,15:21.

[81] 杨皓然,刘丽娜,葛飞,等.基于海马小胶质细胞M1型极化研究逍遥散对OVX联合CUS焦虑抑郁模型大鼠的影响[J].中国中药杂志,2020,45(20):4964.

[82] 刘二军,任首臣,郭庆丰,等.调和阴阳法针灸对老年不寐患者睡眠质量及MT、NE、5-HT水平的影响[J].中国现代医学杂志,2023,33(22):48-53.

[83] 高开英.针灸治疗失眠症疗效及对患者睡眠质量的影响[J].基层医学论坛,2025,29(19):9-12.

[84] 郭鑫,岳增辉,谢菊英,等.针刺对失眠大鼠血清去甲肾上腺素、多巴胺及5-羟色胺含量的影响[J].中国中医药信息杂志,2018,25(4):46.

[85] 吴北峰,彭艳.电项针对睡眠剥夺大鼠脑干5-HT5,5-HIAA,NE含量的影响[J].中医药学报,2011,39(5):85.

[86] 肖伟,章显宝,王震,等.针刺对卒中后抑郁大鼠行为学及海马区神经递质的影响[J].上海针灸杂志,2017,36(6):751-756.

[87] CAI W. Acupuncture and the nervous system[J]. The American journal of Chinese medicine, 1992, 20(03n04): 331-337.

[88] 吴建丽,韩璐,刘旭东,等.不同频率电项针对PCPA致失眠大鼠睡眠时相及血清ACTH、CORT含量的影响[J].吉林中医药,2018,38(2):191.

[89] 刘臻.基于褪黑素及其受体研究电针申脉照海调节失眠大鼠昼夜节律的效应机制[D].上海:上海中医药大学,2014.

[90] 周艳丽,叶险峰.针刺不同腧穴对失眠模型大鼠脑内细胞因子IL-1、TNF-α含量影响的实验研究[J].中国中医基础医学杂志,2012,18(4):419.

[91] Rockstrom MD,Chen L,Taishi P,et al.Tumor necrosis factor alpha in sleep regulation[J].Sleep Med Rev,2018,40:69.

[92] 蔡娲,马文,王观涛,等.电针对脑卒中后抑郁大鼠血清白介素-1β、白介素-6和肿瘤坏死因子-α表达的影响[J].中西医结合心脑血管病杂志,2019,17(22):3515-3518.

基本信息:

DOI:10.13412/j.cnki.zyyl.20260630.002

中图分类号:R285

引用信息:

[1]马骊珠,曹璇,刘煜川,等.中药单体、活性成分、中药复方及中医通过神经-内分泌-免疫系统治疗失眠的作用机制与临床研究进展[J].中药药理与临床().DOI:10.13412/j.cnki.zyyl.20260630.002.

基金信息:

中央引导地方科技发展专项(编号:2025ZY036/YDZX 20206200002673); 甘肃省名中医传承工作室建设项目(批复文号:甘卫中医函[2023] 62号); 甘肃省科技计划项(编号:24YANA007/23YFFA0027/24CXKA009); 高校产业支撑计划项目(编号:2024CYZC-40/2020C-09); 甘肃省中医药科研课题(编号:GZKG-2024-47)

发布时间:

2026-06-30

出版时间:

2026-06-30

网络发布时间:

2026-06-30

检 索 高级检索