
浏览全部资源
扫码关注微信
1.云南中医药大学基础医学院,昆明 650500
2.昆明市中医医院儿科,昆明 650500
3.云南中医药大学科技处,昆明 650500
4.云南中医药大学第一临床医学院儿科,昆明 650500
陈 凤,Email:2022797595@qq.com,研究方向:中医儿科学。
李 刚,Email:1006360333@qq.com。
收稿:2025-12-23,
修回:2026-04-16,
录用:2026-05-09,
纸质出版:2026-07-01
移动端阅览
陈凤, 周晓媛, 牛志超, 等. 变应性鼻炎与情绪障碍共病的神经-免疫机制及中医药干预研究进展[J/OL]. 重庆医科大学学报, 2026,1-7.
Chen Feng,Zhou Xiaoyuan,Niu Zhichao,et al.Research advances in the neuro-immune mechanisms of comorbidity of allergic rhinitis and mood disorders and related traditional Chinese medicine interventions[J].Journal of Chongqing Medical University,
陈凤, 周晓媛, 牛志超, 等. 变应性鼻炎与情绪障碍共病的神经-免疫机制及中医药干预研究进展[J/OL]. 重庆医科大学学报, 2026,1-7. DOI:
Chen Feng,Zhou Xiaoyuan,Niu Zhichao,et al.Research advances in the neuro-immune mechanisms of comorbidity of allergic rhinitis and mood disorders and related traditional Chinese medicine interventions[J].Journal of Chongqing Medical University, DOI:10.13406/j.cnki.cyxb..
变应性鼻炎(allergic rhinitis,AR)是一种全球高发的慢性鼻黏膜炎症性疾病,近年来临床与基础研究均提示其与焦虑、抑郁等情绪障碍存在显著共病关系,严重影响患者生活质量与社会功能。目前,二者共病的病理机制尚未完全阐明,尤其缺乏基于“神经-内分泌-免疫(neuro-endocrine-immune,NEI)网络”的系统性整合分析,临床缺少针对共病的有效干预策略。本文系统综述了AR与情绪障碍共病的多层次发病机制,内容涵盖:①免疫失衡机制,包括辅助性T细胞2(T helper 2 cell,Th2)免疫偏移、上皮屏障损伤与警报素[胸腺基质淋巴细胞生成素(thymic stromal lymphopoietin,TSLP)、白细胞介素(interleukin,IL)-25、IL-33等]释放;②神经内分泌机制,涉及下丘脑-垂体-肾上腺轴(hypothalamic-pituitary-adrenal axis,HPA轴)功能紊乱及神经肽[如P物质(substance P,SP)、降钙素基因相关肽(calcitonin gene-related peptide,CGRP)、血管活性肠肽(vasoactive intestinal peptide,VIP)]分泌异常;③“鼻-脑轴”双向通讯机制,阐释外周炎症通过嗅觉通路影响中枢神经系统,诱发神经炎症与情绪障碍,并形成“外周-中枢-外周”的恶性循环。在治疗方面,重点探讨了中医药干预该共病的多途径潜力:除内服中药及针刺疗法可通过调节免疫、神经内分泌及相关信号通路发挥作用外,芳香疗法也显示出独特优势。然而,现有研究仍较为分散,尤其缺乏针对共病的高质量临床证据与机制整合研究。本文旨在为深入理解AR与情绪障碍共病的NEI网络机制、推动中医药多靶点整合治疗策略的研发提供理论参考与研究思路。
Allergic rhinitis(AR) is a globally prevalent chronic inflammatory disorder of the nasal mucosa. Recent clinical and basic studies have shown that it is significantly comorbid with mood disorders such as anxiety and depression,severely affecting the quality of life and social functioning of patients. The pathological mechanisms underlying this comorbidity remain unclear at present,with a lack of systematic integration analysis based on the neuro-endocrine-immune(NEI) network,and there is also a lack of effective intervention strategies for this comorbidity in clinical practice. This article systematically reviews the multi-level pathogenesis of AR comorbid with mood disorders from the following aspects:(1) immunological imbalance mechanisms,including Th2-skewed immunity,epithelial barrier disruption,and the release of alarmins(such as thymic stromal lymphopoietin,interleukin-25,and interleukin-33);(2)neuroendocrine mechanisms,involving the dysfunction of the hypothalamic-pituitary-adrenal axis and abnormal secretion of neuropeptides(e.g.,substance P,calcitonin gene-related peptide,and vasoactive intestinal peptide);(3)bidirectional communication mechanisms via the “nose-brain axis”,clarifying how peripheral inflammation influences the central nervous system through olfactory pathways,induces neuroinflammation and mood disorders,and forms a vicious “peripheral-central-peripheral” cycle. As for treatment,this article explores the multi-pathway potential of traditional Chinese medicine in managing this comorbidity:oral administration of herbal formulations and acupuncture therapy can exert a therapeutic effect by regulating immunity,neuroendocrine,and related signaling pathways,and aromatherapy has also demonstrated unique advantages. However,existing research remains fragmented,especially with a lack of high-quality clinical evidence and integrated mechanistic studies targeting this comorbidity. This article aims to provide a theoretical reference and research ideas for deepening the understanding of the NEI network mechanisms underlying the comorbidity of AR and mood disorder and promoting the development of multi-target integrated traditional Chinese medicine treatment strategies.
Bernstein JA , Bernstein JS , Makol R , et al . Allergic rhinitis:a review [J ] . Jama , 2024 , 331 ( 10 ): 866 .
张烨铃 , 孙未希 , 彭艳茹 , 等 . 鼻内针治疗变应性鼻炎临床疗效Meta分析 [J ] . 针刺研究 , 2025 , 50 ( 12 ): 1482 - 1494, 后插1-后插6.
Zhang YL , Sun WX , Peng YR , et al . Clinical efficacy of intranasal acupuncture in the treatment of allergic rhinitis:a Meta-analysis [J ] . Acupunct Res , 2025 , 50 ( 12 ): 1482 - 1494, 后插1-后插6.
Wang M , Zhao N , Wang CS , et al . Immunomodulatory properties of mesenchymal stem cells:A potential therapeutic strategy for allergic rhinitis [J ] . Allergy , 2023 , 78 ( 6 ): 1425 - 1440 .
Wang Y , Song XY , Wei SZ , et al . Brain response in allergic rhinitis:Profile and proposal [J ] . J Neurosci Res , 2023 , 101 ( 4 ): 480 - 491 .
Rodrigues J , Franco-Pego F , Sousa-Pinto B , et al . Anxiety and depression risk in patients with allergic rhinitis:a systematic review and meta-analysis [J ] . Rhinology , 2021 , 59 ( 4 ): 360 - 373 .
Salimi M , Ghazvineh S , Zare M , et al . Distraction of olfactory bulb-medial prefrontal cortex circuit may induce anxiety-like behavior in allergic rhinitis [J ] . PLoS One , 2019 , 14 ( 9 ): e0221978 .
Gao YD , Wang ZJ , Ogulur I , et al . The evolution,immunopathogenesis and biomarkers of type 2 inflammation in common allergic disorders [J ] . Allergy , 2025 , 80 ( 7 ): 1848 - 1877 .
Seys SF , Ottaviano G , Tantilipikorn P . Highlights in rhinology [M ] . Frontiers in Allergy : Frontiers Media SA , 2023 .
Liu P , Kang CL , Zhang J , et al . The role of dendritic cells in allergic diseases [J ] . Int Immunopharmacol , 2022 , 113 : 109449 .
Zellweger F , Buschor P , Hobi G , et al . IL-3 but not monomeric IgE regulates FcεRI levels and cell survival in primary human basophils [J ] . Cell Death Dis , 2018 , 9 ( 5 ): 510 .
Yan B , Lan F , Li JY , et al . The mucosal concept in chronic rhinosinusitis:Focus on the epithelial barrier [J ] . J Allergy Clin Immunol , 2024 , 153 ( 5 ): 1206 - 1214 .
Hong HY , Liao SM , Chen FH , et al . Role of IL-25,IL-33,and TSLP in triggering united airway diseases toward type 2 inflammation [J ] . Allergy , 2020 , 75 ( 11 ): 2794 - 2804 .
Li XT , Guo JJ , Song J , et al . Targeting thymic stromal lymphopoietin in nasal type 2 inflammation [J ] . Eye ENT Res , 2025 , 2 ( 3 ): 164 - 172 .
Borgia F , Custurone P , Li Pomi F , et al . IL-33 and IL-37:a possible axis in skin and allergic diseases [J ] . Int J Mol Sci , 2023 , 24 ( 1 ): 372 .
Jia M , Lei XC , Jiang FW , et al . The regulatory effects of luteolin,calycosin,and formononetin on the NLRP3/IL-33/ILC2s axis in the treatment of allergic rhinitis:mechanistic analysis and therapeutic potential [J ] . Front Pharmacol , 2025 , 16 : 1658772 .
Chang WC , Lv H , Tan L , et al . Downregulation of deubiquitinating enzyme USP25 promotes the development of allergic rhinitis by enhancing TSLP signaling in the nasal epithelium [J ] . Mol Med Rep , 2022 , 26 ( 5 ): 347 .
Zhang H , Zhu XH , Liu X , et al . Long non-coding RNA FOXD3-AS1 regulates the expression and secretion of IL-25 in nasal epithelial cells to inhibit Th2 type immunoreaction in allergic rhinitis [J ] . Mol Cell Biochem , 2020 , 473 ( 1 ): 239 - 246 .
Yang SS , Wu J , Zhang QX , et al . Catgut implantation at acupoint reduces immune reaction in a rat model of allergic rhinitis [J ] . Evid Based Complementary Altern Med , 2018 , 2018 : 7629239 .
Duan TH , Du Y , Xing CS , et al . Toll-like receptor signaling and its role in cell-mediated immunity [J ] . Front Immunol , 2022 , 13 : 812774 .
Manik MK , Pan MQ , Xiao L , et al . Structural basis for TIR domain-mediated innate immune signaling by Toll-like receptor adaptors TRIF and TRAM [J ] . Proc Natl Acad Sci U S A , 2025 , 122 ( 2 ): e2418988122 .
Zhang M , Wu D , Liu LX , et al . Role of Toll-like receptor 2/NF-κB signaling pathway in the pathogenesis of allergic rhinitis [J ] . Int J Clin Exp Med , 2019 , 12 ( 7 ): 8702 - 8709 .
杨莎莎 , 曾 斌 , 刘代恩 , 等 . 穴位埋线治疗变应性鼻炎的神经免疫联动机制研究 [J ] . 中华中医药学刊 , 2017 , 35 ( 10 ): 2480 - 2484 , I0002 - I0006 .
Yang SS , Zeng B , Liu DE , et al . Effects of catgut implantation at acupoints on neural immune linkage of rats with allergic rhinitis [J ] . Chin Arch Tradit Chin Med , 2017 , 35 ( 10 ): 2480 - 2484 , I0002 - I0006 .
Veiga-Fernandes H , Mucida D . Neuro-immune interactions at barrier surfaces [J ] . Cell , 2016 , 165 ( 4 ): 801 - 811 .
Klimov V , Cherevko N , Klimov A , et al . Neuronal-immune cell units in allergic inflammation in the nose [J ] . Int J Mol Sci , 2022 , 23 ( 13 ): 6938 .
蔡诗茹 , 娄鸿飞 . 变应性鼻炎的神经免疫调节机制 [J ] . 临床耳鼻咽喉头颈外科杂志 , 2021 , 35 ( 9 ): 859 - 864 .
Cai SR , Lou HF . Neuroimmunomodulation in allergic rhinitis [J ] . J Clin Otorhinolaryngol Head Neck Surg , 2021 , 35 ( 9 ): 859 - 864 .
Hueston CM , Deak T . The inflamed axis:The interaction between stress,hormones,and the expression of inflammatory-related genes within key structures comprising the hypothalamic-pituitary-adrenal axis [J ] . Physiol Behav , 2014 , 124 : 77 - 91 .
Podgorny OV , Gulyaeva NV . Glucocorticoid-mediated mechanisms of hippocampal damage:Contribution of subgranular neurogenesis [J ] . J Neurochem , 2021 , 157 ( 3 ): 370 - 392 .
木艾塔尔·艾斯卡尔 , 阿依孜木姑·阿卜杜外力 , 马依热·努尔买卖提 , 等 . 中药缓溃乐对溃疡性结肠炎小鼠HPA轴和5-HT信号通路相关分子的影响 [J ] . 现代生物医学进展 , 2024 , 24 ( 4 ): 617 - 623 .
MUAITAER·Aisikaer , AYIZIMUGULI· Abuduwaili , MAYIRE· Nuermaimaiti , et al . The effect of Huan Kui le on HPA axis and 5-HT signal pathway related molecules in UC mice [J ] . Prog Mod Biomed , 2024 , 24 ( 4 ): 617 - 623 .
Taves MD , Ashwell JD . Glucocorticoids in T cell development,differentiation and function [J ] , Nat Rev Immunol , 2021 , 21 ( 4 ): 233 - 243 .
Hashimoto M , Sato EF , Hiramoto K , et al . Role of the hypothalamo-pituitary-adrenal axis in the modulation of pollinosis induced by pollen antigens [J ] . Allergol Int , 2010 , 59 ( 2 ): 201 - 206 .
程冯丽 . 时钟基因Period2调控小鼠鼻过敏反应昼夜时相变化的机制研究 [D ] . 太原 : 山西医科大学 , 2020 .
Cheng FL . Study on the mechanism of clock gene Period2 regulating the diurnal phase change of nasal allergic reaction in mice [D ] . Taiyuan : Shanxi Medical University , 2020 .
Nakamura Y , Harama D , Shimokawa N , et al . Circadian clock gene Period2 regulates a time-of-day–dependent variation in cutaneous anaphylactic reaction [J ] . J Allergy Clin Immunol , 2011 , 127 ( 4 ): 1038 - 1045 . e3.
Yang SS , Wu J , Zhang QX , et al . Allergic rhinitis in rats is associated with an inflammatory response of the hippocampus [J ] . Behav Neurol , 2018 , 2018 : 8750464 .
Wang J , Xiao DQ , Chen HY , et al . Cumulative evidence for association of rhinitis and depression [J ] . Allergy Asthma Clin Immunol , 2021 , 17 ( 1 ): 111 .
Gray JD , Kogan JF , Marrocco J , et al . Genomic and epigenomic mechanisms of glucocorticoids in the brain [J ] . Nat Rev Endocrinol , 2017 , 13 ( 11 ): 661 - 673 .
Vásquez-Pérez JM , González-Guevara E , Gutiérrez-Buenabad D , et al . Is nasal dysbiosis a required component for neuroinflammation in major depressive disorder? [J ] . Mol Neurobiol , 2025 , 62 ( 2 ): 2459 - 2469 .
Chen S , Qu SH , Zhang Y , et al . Impact of acupuncture for allergic rhinitis on the activity of the hypothalamus-pituitary-adrenal axis:study protocol for a randomized controlled trial [J ] . Trials , 2019 , 20 ( 1 ): 372 .
Kang JL , Zhongming DU , Guo W , et al . Effect of acupuncture on serum levels of hypothalamic-pituitary-adrenal axis related hormones and immune factors in rats with allergic rhinitis [J ] . J Tradit Chin Med , 2025 , 45 ( 2 ): 359 - 367 .
杜钟名 . 针刺治疗常年性变应性鼻炎的临床疗效和机制研究 [D ] . 北京 : 北京中医药大学 , 2023 .
Du ZM . Clinical Efficacy and Mechanism of Acupuncture in the Treatment of Perennial Allergic Rhinitis . Beijing : Beijing University of Chinese Medicine , 2023 .
Chattopadhyay S , Chakraborty S , Maity SC , et al . Nasal route:a breakthrough for drug delivery [J ] . J Pharm Negat Results , 2022 : 315 - 334 .
Voisin T , Bouvier A , Chiu IM . Neuro-immune interactions in allergic diseases:novel targets for therapeutics [J ] . Int Immunol , 2017 , 29 ( 6 ): 247 - 261 .
Ito A , Hagiyama M , Oonuma J . Nerve-mast cell and smooth muscle-mast cell interaction mediated by cell adhesion molecule-1,CADM1 [J ] . J Smooth Muscle Res , 2008 , 44 ( 2 ): 83 - 93 .
Cong JC , Lv H , Xu Y . The role of nociceptive neurons in allergic rhinitis [J ] . Front Immunol , 2024 , 15 : 1430760 .
Jean EE , Good O , Rico JMI , et al . Neuroimmune regulatory networks of the airway mucosa in allergic inflammatory disease [J ] . J Leukoc Biol , 2022 , 111 ( 1 ): 209 - 221 .
康 瑞 , 程冯丽 , 赵长青 . 变应性鼻炎神经-免疫机制的研究进展 [J ] . 中国耳鼻咽喉颅底外科杂志 , 2023 , 29 ( 3 ): 121 - 126 .
Kang R , Cheng FL , Zhao CQ . Research progress of the neuro-immune mechanism in allergic rhinitis [J ] . Chin J Otorhinolaryngol Skull Base Surg , 2023 , 29 ( 3 ): 121 - 126 .
Zhou Y , Chen R , Kong LL , et al . Neuroimmune communication in allergic rhinitis [J ] . Front Neurol , 2023 , 14 : 1282130 .
Wu WH , Li JN , Chen S , et al . The airway neuro-immune axis as a therapeutic target in allergic airway diseases [J ] . Respir Res , 2024 , 25 ( 1 ): 83 .
Meng YF , Lu HS , Wang CS , et al . Naso -ocular neuropeptide interactions in allergic rhinoconjunctivitis,rhinitis,and conjunctivitis [J ] . World Allergy Organ J , 2021 , 14 ( 5 ): 100540 .
Gellrich D , Pfab F , Ortiz M , et al . Acupuncture and its effect on cytokine and chemokine profiles in seasonal allergic rhinitis:a preliminary three-armed,randomized,controlled trial [J ] . Eur Arch Oto Rhino Laryngol , 2022 , 279 ( 10 ): 4985 - 4995 .
范雪琪 , 邱彩霞 , 颜水平 , 等 . 基于鼻黏膜-海马神经免疫机制探讨醒鼻凝胶滴鼻剂对变应性鼻炎大鼠的影响 [J ] . 康复学报 , 2024 , 34 ( 4 ): 361 - 369 .
Fan XQ , Qiu CX , Yan SP , et al . Effect of xingbi gel nasal drops on rats with allergic rhinitis based on the nasal mucosa-hippocampus neuroimmune mechanism [J ] . Rehabil Med , 2024 , 34 ( 4 ): 361 - 369 .
Tanaka Y , Furuta A , Asano K , et al . Modulation of Th1/Th2 cytokine balance by quercetin in vitro [J ] . Medicines , 2020 , 7 ( 8 ): 46 .
Sakai-Kashiwabara M , Asano K . Inhibitory action of quercetin on eosinophil ActivationIn vitro [J ] . Evid Based Complementary Altern Med , 2013 , 2013 : 127105 .
董博洋 , 李丙泉 , 李 岩 . 鼻内针刺联合调神针治疗中重度持续性变应性鼻炎的临床疗效 [J ] . 针刺研究 , 2024 , 49 ( 9 ): 964 - 971 .
Dong BY , Li BQ , Li Y . Clinical efficacy of intranasal acupuncture combined with Tiaoshen acupuncture in the treatment of moderate-to-severe persistent allergic rhinitis [J ] . Acupunct Res , 2024 , 49 ( 9 ): 964 - 971 .
Ebrahim Soltani Z , Badripour A , Haddadi NS , et al . Allergic rhinitis in BALB/c mice is associated with behavioral and hippocampus changes and neuroinflammation via the TLR4/NF-κB signaling pathway [J ] . Int Immunopharmacol , 2022 , 108 : 108725 .
Leon M , Troscianko ET , Woo CC . Inflammation and olfactory loss are associated with at least 139 medical conditions [J ] . Front Mol Neurosci , 2024 , 17 : 1455418 .
Jiménez A , Sánchez-Hernández JD , Maya-López V , et al . Interleukin-1β depresses neuronal activity in the rat olfactory bulb even during odor stimulation [J ] . PLoS One , 2025 , 20 ( 9 ): e0332592 .
Mou YK , Sun CY , Wei SZ , et al . P2X7 receptor of olfactory bulb microglia plays a pathogenic role in stress-related depression in mice with allergic rhinitis [J ] . Neurobiol Dis , 2024 , 192 : 106432 .
Lv H , Liu PQ , Zhou FW , et al . TAK-242 ameliorates olfactory dysfunction in a mouse model of allergic rhinitis by inhibiting neuroinflammation in the olfactory bulb [J ] . Int Immunopharmacol , 2021 , 92 : 107368 .
Guo JS , Lei L , Yang HB , et al . Effects of nasal allergens and environmental particulate matter on brainstem metabolites and the consequence of brain-spleen axis in allergic rhinitis [J ] . Environ Int , 2024 , 190 : 108890 .
LaFever BJ , Imamura F . Effects of nasal inflammation on the olfactory bulb [J ] . J Neuroinflammation , 2022 , 19 ( 1 ): 294 .
Lan YA , Guo JX , Yao MH , et al . The role of neuro-immune interactions in the pathology and pathogenesis of allergic rhinitis [J ] . Immunol Investig , 2024 , 53 ( 7 ): 1013 - 1029 .
Zhou Y , Chen BJ , Fu Y , et al . Cang-ai volatile oil alleviates nasal inflammation via Th1/Th2 cell imbalance regulation in a rat model of ovalbumin-induced allergic rhinitis [J ] . Front Pharmacol , 2024 , 15 : 1332036 .
Chen BJ , Li JJ , Xie YH , et al . Cang-ai volatile oil improves depressive-like behaviors and regulates DA and 5-HT metabolism in the brains of CUMS-induced rats [J ] . J Ethnopharmacol , 2019 , 244 : 112088 .
Choi SY , Park K . Effect of inhalation of aromatherapy oil on patients with perennial allergic rhinitis:a randomized controlled trial [J ] . Evid Based Complementary Altern Med , 2016 , 2016 : 7896081 .
Geng B , Dilley M , Anterasian C . Biologic therapies for allergic rhinitis and nasal polyposis [J ] . Curr Allergy Asthma Rep , 2021 , 21 ( 6 ): 36 .
Dong BY , Xie LZ , Li Y . Exploring the therapeutic role of natural products in allergic rhinitis based on pathophysiology and signaling pathways [J ] . J Asthma Allergy , 2025 , 18 : 1551 - 1584 .
Chu SD . Sixty cases of refractory allergic rhinitis treated by vidian trunk or branch neurectomy:A single-center observational study [J ] . Medicine , 2022 , 101 ( 45 ): e31704 .
Xu HP , Shi XY , Li X , et al . Neurotransmitter and neuropeptide regulation of mast cell function:a systematic review [J ] . J Neuroinflammation , 2020 , 17 ( 1 ): 356 .
Song HX , Yang AH , Wang Y , et al . Potential roles of inhalation aromatherapy on stress-induced depression by inhibiting inflammation in the peripheral olfactory system [J ] . Neurochem Int , 2025 , 186 : 105967 .
0
浏览量
0
下载量
0
CSCD
关联资源
相关文章
相关作者
相关机构
京公网安备11010802024621