中药基于“免疫–神经”双调节机制缓解 抑郁症——聚焦NLRP3/TLR4通路及pH响应递送策略的研究进展
Traditional Chinese Medicine Alleviates Depression Based on the “Immuno-Neural” Dual-Regulation Mechanism—Research Progress Focusing on the NLRP3/TLR4 Pathway and pH-Responsive Delivery Strategies
摘要: 抑郁症是一种发病率较高的精神障碍性疾病,神经免疫炎症在其发生与发展中具有重要作用。NLRP3/TLR4介导的炎症通路可激活小胶质细胞、释放促炎细胞因子,并通过改变神经递质代谢和神经可塑性,成为连接外周免疫与中枢神经免疫的关键环节。中药及其活性成分通过多靶点、多通路协同调节该通路,从而实现“免疫–神经”双向调节并发挥重要作用。本文详细介绍了NLRP3/TLR4介导的抑郁症神经免疫调控机制,重点阐述了中药活性成分与复方抑制该通路以减轻神经炎症、保护神经元功能的研究现状,并针对现有给药方式存在的生物利用度低、靶向性差等问题,介绍了PH响应型递送系统在中药抗抑郁精准递送中的应用。综上,本文为基于“免疫–神经”双调节机制的中药抗抑郁提供了理论指导,也为PH响应递送策略的研究提供了参考。
Abstract: Depression is a highly prevalent psychiatric disorder, in which neuroimmune inflammation plays a critical role in its onset and progression. The NLRP3/TLR4-mediated inflammatory pathway, by activating microglia and releasing pro-inflammatory cytokines, as well as altering neurotransmitter metabolism and neuroplasticity, serves as a key link connecting peripheral immunity and central neuroimmune regulation. Traditional Chinese medicine (TCM) and its active components, through multi-target and multi-pathway synergistic regulation of this pathway, achieve “immuno-neural” bidirectional regulation and exert significant therapeutic effects. This review provides a detailed overview of the neuroimmune regulatory mechanisms of the NLRP3/TLR4 pathway in depression, with a focus on current research progress regarding how TCM active components and formulas inhibit this pathway to alleviate neuroinflammation and protect neuronal function. Furthermore, in view of the limitations of current administration routes, such as low bioavailability and poor targeting, this review also introduces the application of pH-responsive delivery systems for the precise delivery of TCM antidepressants. In summary, this review provides a theoretical basis for TCM antidepressant research based on the “immuno-neural” dual-regulation mechanism and offers a reference for the development of pH-responsive delivery strategies.
文章引用:滕晋, 高喆, 曹相玫. 中药基于“免疫–神经”双调节机制缓解 抑郁症——聚焦NLRP3/TLR4通路及pH响应递送策略的研究进展[J]. 临床医学进展, 2026, 16(5): 1394-1407. https://doi.org/10.12677/acm.2026.1651941

参考文献

[1] GBD 2019 Mental Disorders Collaborators (2022) Global, Regional, and National Burden of 12 Mental Disorders in 204 Countries and Territories, 1990-2019: A Systematic Analysis for the Global Burden of Disease Study 2019. The Lancet Psychiatry, 9, 137-150.
[2] GBD 2019 Diseases and Injuries Collaborators (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] [PubMed]
[3] Rifkin-Zybutz, R., MacNeill, S., Davies, S.J., Dickens, C., Campbell, J., Anderson, I.M., et al. (2020) Does Anxiety Moderate the Effectiveness of Mirtazapine in Patients with Treatment-Resistant Depression? A Secondary Analysis of the MIR Trial. Journal of Psychopharmacology, 34, 1342-1349. [Google Scholar] [CrossRef] [PubMed]
[4] Bulek, D. and BaDour, S. (2026) From Monoamine Deficits to Multiscale Plasticity: Twenty-Five Years of Ketamine and the Neurophysiology of Depression. Journal of Neurophysiology, 135, 406-413. [Google Scholar] [CrossRef
[5] Jiao, W., Lin, J., Deng, Y., Ji, Y., Liang, C., Wei, S., et al. (2025) The Immunological Perspective of Major Depressive Disorder: Unveiling the Interactions between Central and Peripheral Immune Mechanisms. Journal of Neuroinflammation, 22, Article No. 10. [Google Scholar] [CrossRef] [PubMed]
[6] Han, Q., Li, W., Chen, P., Wang, L., Bao, X., Huang, R., et al. (2024) Microglial NLRP3 Inflammasome-Mediated Neuroinflammation and Therapeutic Strategies in Depression. Neural Regeneration Research, 19, 1890-1898. [Google Scholar] [CrossRef] [PubMed]
[7] He, X.M., Zhang, Y., Chen, C.Y., et al. (2026) P2X7 Receptor-Mediated cGAS-STING Pathway Activation Underlies Chronic Stress-Induced Depressive-Like Behaviors. Purinergic Signalling, 22, Article No. 35. [Google Scholar] [CrossRef
[8] Li, Y.K., Chen, J.G. and Wang, F. (2021) The Emerging Roles of Absent in Melanoma 2 (AIM2) Inflammasome in Central Nervous System Disorders. Neurochemistry International, 149, Article 105122. [Google Scholar] [CrossRef] [PubMed]
[9] Chen, K.Q., Tang, W.R. and Liu, X. (2025) Research and Progress of cGAS/STING/NLRP3 Signaling Pathway: A Mini Review. Frontiers in Immunology, 16, Article 1594133. [Google Scholar] [CrossRef] [PubMed]
[10] Mac Giollabhui, N., Ng, T.H., Ellman, L.M. and Alloy, L.B. (2021) The Longitudinal Associations of Inflammatory Biomarkers and Depression Revisited: Systematic Review, Meta-Analysis, and Meta-Regression. Molecular Psychiatry, 26, 3302-3314. [Google Scholar] [CrossRef] [PubMed]
[11] Lv, S., Kong, L., Zhong, X., Shang, R., Lu, Y., Zhang, G., et al. (2025) Natural Antidepressants in Neuroimmunomodulation: Molecular Mechanisms, Action Targets, and Therapeutic Potential. Frontiers in Immunology, 16, Article 1642001. [Google Scholar] [CrossRef
[12] 彭放, 王磊, 彭璐. 用爱为患者疗伤——中国抗癌协会肿瘤心理专业委员会2019学术年会在长举行[N/OL]. 长沙晚报网.
https://hnca.org.cn/cpos/mt/a_111937.html, 2026-04-02.
[13] Balachandran, R., Thaysen, H.V., Christensen, P., Zachariae, R. and Iversen, L.H. (2023) Biopsychosocial Late Effects after Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Metastases from Colorectal and Appendiceal Cancer: A National Prospective Cohort Study. Annals of Surgical Oncology, 31, 1959-1969. [Google Scholar] [CrossRef] [PubMed]
[14] Simonetti, A., Grisoni, F., Restaino, A., Calderoni, C., Camardese, G., Donofrio, A.M., et al. (2025) Real-World Use, Effectiveness and Tolerability of Antidepressant Treatment in Oncology Patients. Psycho-Oncology, 34, e70340. [Google Scholar] [CrossRef
[15] Morone, D., Autilia, F.D., Schorn, T., Erreni, M. and Doni, A. (2020) Evaluation of Cell Metabolic Adaptation in Wound and Tumour by Fluorescence Lifetime Imaging Microscopy. Scientific Reports, 10, Article No. 6289. [Google Scholar] [CrossRef] [PubMed]
[16] Eissa, E.M., El Sisi, A.M., Bekhet, M.A., El-Ela, F.I.A., Kharshoum, R.M., Ali, A.A., et al. (2024) pH-Sensitive in Situ Gel of Mirtazapine Invasomes for Rectal Drug Delivery: Protruded Bioavailability and Anti-Depressant Efficacy. Pharmaceuticals, 17, Article 978. [Google Scholar] [CrossRef] [PubMed]
[17] Che, L., Xie, J., Xia, C. and Yu, Q. (2026) Traditional Chinese Medicine Ameliorates Depression via the Gut-Brain Axis: A Review Focus on NLRP3/TLR4-Mediated Inflammatory Pathways and Gut Microbiota Modulation. Neuropsychiatric Disease and Treatment, 22, 1-15. [Google Scholar] [CrossRef
[18] Guo, X., Liu, H., Song, Y., Wang, J., Liu, D., Zheng, Z., et al. (2026) Neuro-Immune Crosstalk: Molecular Mechanisms, Biological Functions, Diseases, and Therapeutic Targets. MedComm, 7, e70497. [Google Scholar] [CrossRef
[19] Ball, J.B., Green-Fulgham, S.M. and Watkins, L.R. (2022) Mechanisms of Microglia-Mediated Synapse Turnover and Synaptogenesis. Progress in Neurobiology, 218, Article 102336. [Google Scholar] [CrossRef] [PubMed]
[20] Yeo, X.Y., Choi, Y., Hong, Y., Kwon, H.N. and Jung, S. (2025) Contemporary Insights into Neuroimmune Interactions across Development and Aging. Frontiers in Neurology, 16, Article 1611124. [Google Scholar] [CrossRef] [PubMed]
[21] Lee, S.Y. and Chung, W. (2024) Astrocytic Crosstalk with Brain and Immune Cells in Healthy and Diseased Conditions. Current Opinion in Neurobiology, 84, Article 102840. [Google Scholar] [CrossRef] [PubMed]
[22] Sun, X., Zhang, F., Wang, L., Lee, G., Yang, S., Zhou, D., et al. (2025) Immunological Microenvironment and Targeted Therapeutics in Multiple Sclerosis: New Insights in Crosstalk between Immune Niches and CNS. Frontiers in Immunology, 16, Article 1604987. [Google Scholar] [CrossRef] [PubMed]
[23] Köhler, C.A., Freitas, T.H., Stubbs, B., Maes, M., Solmi, M., Veronese, N., et al. (2017) Peripheral Alterations in Cytokine and Chemokine Levels after Antidepressant Drug Treatment for Major Depressive Disorder: Systematic Review and Meta-Analysis. Molecular Neurobiology, 55, 4195-4206. [Google Scholar] [CrossRef] [PubMed]
[24] Pandey, G.N., Zhang, H., Sharma, A. and Ren, X. (2021) Innate Immunity Receptors in Depression and Suicide: Upregulated NOD-Like Receptors Containing Pyrin (NLRPs) and Hyperactive Inflammasomes in the Postmortem Brains of People Who Were Depressed and Died by Suicide. Journal of Psychiatry and Neuroscience, 46, E538-E547. [Google Scholar] [CrossRef] [PubMed]
[25] Pak, T., Haque, N. and Jha, M.K. (2025) Lessons from Clinical Trials of Immunomodulatory Drugs in Psychiatric Disorders. Biological Psychiatry, 99, 1025-1051. [Google Scholar] [CrossRef
[26] Gong, X., Chang, R., Zou, J., Tan, S. and Huang, Z. (2022) The Role and Mechanism of Tryptophan—Kynurenine Metabolic Pathway in Depression. Reviews in the Neurosciences, 34, 313-324. [Google Scholar] [CrossRef] [PubMed]
[27] Savonije, K., Meek, A. and Weaver, D.F. (2023) Indoleamine 2,3-Dioxygenase as a Therapeutic Target for Alzheimer’s Disease and Geriatric Depression. Brain Sciences, 13, Article 852. [Google Scholar] [CrossRef] [PubMed]
[28] Weston, F.I., Sforzini, L., Cattaneo, A. and Pariante, C.M. (2023) Neuroendocrine-Immune Interactions in Major Depressive Disorder: Glucocorticoids and Glucocorticoid Receptors. In: Masterclass in Neuroendocrinology, Springer, 135-157. [Google Scholar] [CrossRef
[29] Markova, E.V., Knyazheva, M.A., Tikhonova, M.A. and Amstislavskaya, T.G. (2022) Structural and Functional Characteristics of the Hippocampus in Depressive-Like Recipients after Transplantation of in Vitro Caffeine-Modulated Immune Cells. Neuroscience Letters, 786, Article 136790. [Google Scholar] [CrossRef] [PubMed]
[30] Gu, S., Li, Y., Jiang, Y., Huang, J.H. and Wang, F. (2022) Glymphatic Dysfunction Induced Oxidative Stress and Neuro-Inflammation in Major Depression Disorders. Antioxidants, 11, Article 2296. [Google Scholar] [CrossRef] [PubMed]
[31] Tyagi, R. and Bartley, C.M. (2025) Dynamic Cytokine Relationships across the Blood-Brain Barrier in Humans and Nonhuman Primates, Implications for Psychiatric Illness: A Systematic Review. Biological Psychiatry, 2025, 1-19. [Google Scholar] [CrossRef
[32] Ding, L., Xue, L., Cheng, C., Tang, K., Chen, Z. and Du, G. (2025) The NLRP3 Inflammasome in Depression: A Narrative Review from Neuroinflammation to Novel Therapeutic Approaches. Brain Research Bulletin, 232, Article 111592. [Google Scholar] [CrossRef
[33] Fu, J. and Wu, H. (2023) Structural Mechanisms of NLRP3 Inflammasome Assembly and Activation. Annual Review of Immunology, 41, 301-316. [Google Scholar] [CrossRef] [PubMed]
[34] Li, Y., Du, L., He, X. and Liang, Z. (2026) Molecular Pathways of Traditional Chinese Medicine-Derived Compounds in Cognitive Decline and Depressive Disorders: Neuroinflammation, Synaptic Plasticity and Stress Axis Regulation. Pakistan Journal of Pharmaceutical Sciences, 39, 1350-1366.
[35] Li, Y., Chen, X., Zhou, M., Feng, S., Peng, X. and Wang, Y. (2024) Microglial TLR4/NLRP3 Inflammasome Signaling in Alzheimer’s Disease. Journal of Alzheimers Disease, 97, 75-88. [Google Scholar] [CrossRef] [PubMed]
[36] Wang, L., Li, H., Zhao, Y., Sun, X., Qian, M., Shao, F., et al. (2025) Artemisinin Alleviates Chronic Social Defeat Stress-Induced Depressive-Like Behavior by Inhibiting Neuroinflammation via the TLR4/MyD88/NF-κB/NLRP3 Signaling Pathway. Phytotherapy Research, 39, 5263-5281. [Google Scholar] [CrossRef
[37] Song, M.T., Ruan, J., Zhang, R.Y., Deng, J., Ma, Z.Q. and Ma, S.P. (2018) Astragaloside IV Ameliorates Neuroinflammation-Induced Depressive-Like Behaviors in Mice via the PPARγ/NF-κB/NLRP3 Inflammasome Axis. Acta Pharmacologica Sinica, 39, 1559-1570. [Google Scholar] [CrossRef] [PubMed]
[38] Liu, X., Wang, S., Wu, X., Zhao, Z., Jian, C., Li, M., et al. (2024) Astragaloside IV Alleviates Depression in Rats by Modulating Intestinal Microbiota, T-Immune Balance, and Metabolome. Journal of Agricultural and Food Chemistry, 72, 259-273. [Google Scholar] [CrossRef] [PubMed]
[39] 朱岳, 黄东梅, 鞠营辉, 王梦琳, 吴睿. 基于网络药理学和分子对接技术探讨黄芪甲苷抗抑郁的作用机制[J]. 现代药物与临床, 2022, 37(11): 2465-2474.
[40] Han, D., Zhao, Z., Mao, T., Gao, M., Yang, X. and Gao, Y. (2024) Ginsenoside Rg1: A Neuroprotective Natural Dammarane-Type Triterpenoid Saponin with Anti-Depressive Properties. CNS Neuroscience & Therapeutics, 30, e70150. [Google Scholar] [CrossRef] [PubMed]
[41] Zhuang, S., Shi, F., Cannella, N., Ubaldi, M., Ciccocioppo, R., Li, H., et al. (2025) Pharmacological Mechanism and Drug Research Prospects of Ginsenoside Rb1 as an Antidepressant. Antioxidants, 14, Article 238. [Google Scholar] [CrossRef] [PubMed]
[42] Guo, Y., Xie, J., Zhang, L., Yang, L., Ma, J., Bai, Y., et al. (2021) Ginsenoside Rb1 Exerts Antidepressant-Like Effects via Suppression Inflammation and Activation of AKT Pathway. Neuroscience Letters, 744, Article 135561. [Google Scholar] [CrossRef] [PubMed]
[43] Jin, X., Liu, M., Zhang, D., Zhong, X., Du, K., Qian, P., et al. (2019) Baicalin Mitigates Cognitive Impairment and Protects Neurons from Microglia-Mediated Neuroinflammation via Suppressing NLRP3 Inflammasomes and TLR4/NF-κB Signaling Pathway. CNS Neuroscience & Therapeutics, 25, 575-590. [Google Scholar] [CrossRef] [PubMed]
[44] Liu, B., Peng, Y., Wang, C., Wei, H., Xu, S., Liu, Y., et al. (2025) Baicalin Prevents Experimental Autoimmune Uveitis by Promoting Macrophage Polarization Balance through Inhibiting the HIF-1α Signaling Pathway. Scientific Reports, 15, Article No. 16424. [Google Scholar] [CrossRef] [PubMed]
[45] Lee, M.N., Lee, Y., Wu, D. and Pae, M. (2021) Luteolin Inhibits NLRP3 Inflammasome Activation via Blocking ASC Oligomerization. The Journal of Nutritional Biochemistry, 92, Article 108614. [Google Scholar] [CrossRef] [PubMed]
[46] Zhang, Y.C., Gan, F.F., Shelar, S.B., Ng, K.Y. and Chew, E.H. (2013) Antioxidant and Nrf2 Inducing Activities of Luteolin, a Flavonoid Constituent in Ixeris Sonchifolia Hance, Provide Neuroprotective Effects against Ischemia-Induced Cellular Injury. Food and Chemical Toxicology, 59, 272-280. [Google Scholar] [CrossRef] [PubMed]
[47] 胡洋, 潘韵铮, 李庆菊, 郑仕中, 等. 丹酚酸B通过抑制NLRP3炎症小体Priming阶段减轻缺氧诱导大鼠心肌细胞损伤[J]. 中国药理学通报, 2020, 36(2): 210-215.
[48] 付宏鑫, 殷思敏, 官学苹, 江嘉颖, 等. 丹酚酸B抑制HMGB1/TLR4/NF-κB通路改善顺铂诱导的急性肾损伤[J]. 中药材, 2023, 46(9): 2291-2295.
[49] 聂窈, 孙宇婷, 徐焕华, 王宇光, 等. 阿魏酸抑制NLRP3炎症小体减轻辐射诱导的AHH-1细胞炎症[J]. 中药药理与临床, 2020, 36(1): 63-68.
[50] 黄倩倩. 阿魏通过调控PI3K/Akt/GSK3β/Nrf2/HO-1通路改善氧化应激和凋亡发挥神经保护作用[D]: [博士学位论文]. 北京: 北京中医药大学, 2022.
[51] 郑姣, 罗新辉, 穆歌, 谢素贞, 赵欢欢. 阿魏酸钠对氧诱导视网膜病变小鼠肺组织损伤的影响[J]. 遵义医科大学学报, 2022, 45(6): 754-760.
[52] Qin, Z., Shi, D., Li, W., Cheng, D., Zhang, Y., Zhang, S., et al. (2023) Berberine Ameliorates Depression-Like Behaviors in Mice via Inhibiting NLRP3 Inflammasome-Mediated Neuroinflammation and Preventing Neuroplasticity Disruption. Journal of Neuroinflammation, 20, Article No. 54. [Google Scholar] [CrossRef] [PubMed]
[53] Li, J., Lv, L., Hu, M., Liu, Z. and Zhou, S. (2025) Inhibition of N6-Methyladenosine Methylation of ASC by Berberine Ameliorates Pyroptosis of Renal Tubular Epithelial Cells in Acute Kidney Injury. Cellular Signalling, 131, Article 111732. [Google Scholar] [CrossRef] [PubMed]
[54] Cheng, R., Song, A., Jiang, J., Qiaolongbatu, X., Wu, Z., Qian, F., et al. (2025) Berberine Alleviates Chronic Restraint Stress-Induced Depression-Like Behavior by Modulating Gut Microbiota and SCFA Production in Mice. Biotechnology and Applied Biochemistry, 73, 537-550. [Google Scholar] [CrossRef
[55] Cheng, J., Chen, M., Wan, H., Chen, X., Li, C., Zhu, J., et al. (2021) Paeoniflorin Exerts Antidepressant-Like Effects through Enhancing Neuronal FGF-2 by Microglial Inactivation. Journal of Ethnopharmacology, 274, Article 114046. [Google Scholar] [CrossRef] [PubMed]
[56] Tian, D., Wang, M., Liu, A., Gao, M., Qiu, C., Yu, W., et al. (2020) Antidepressant Effect of Paeoniflorin Is through Inhibiting Pyroptosis CASP-11/GSDMD Pathway. Molecular Neurobiology, 58, 761-776. [Google Scholar] [CrossRef] [PubMed]
[57] Zhu, H.Z., Liang, Y.D., Hao, W.Z., Ma, Q.Y., Li, X.J., Li, Y.M. and Chen, J.X. (2021) Xiaoyaosan Exerts Therapeutic Effects on the Colon of Chronic Restraint Stress Model Rats via the Regulation of Immunoinflammatory Activation Induced by the TLR4/NLRP3 Inflammasome Signaling Pathway. Evidence-Based Complementary and Alternative Medicine, 2021, 1-18. [Google Scholar] [CrossRef] [PubMed]
[58] 朱文俊, 黄敏仪, 袁艿君, 马庆宇, 陈家旭. 逍遥散抑制NLRP3炎症小体诱导神经炎症治疗抑郁症研究进展[J]. 中国中医基础医学杂志, 2024, 30(10): 1667-1671.
[59] Liu, X., Liu, H., Wu, X., Zhao, Z., Wang, S., Wang, H., et al. (2024) Xiaoyaosan against Depression through Suppressing LPS Mediated TLR4/NLRP3 Signaling Pathway in “Microbiota-Gut-Brain” Axis. Journal of Ethnopharmacology, 335, Article 118683. [Google Scholar] [CrossRef] [PubMed]
[60] Chen, C., Yu, R., Xue, Z., Yan, Z.Y., et al. (2020) Xiaoyaosan Improves Depressive-Like Behaviors by Regulating the NLRP3 Signaling Pathway in the Rat Cerebral Cortex. Journal of Traditional Chinese Medical Sciences, 7, 265-273. [Google Scholar] [CrossRef
[61] Zhang, B., Ji, J., Zhang, X., Yu, X., Hu, X., Liu, J., et al. (2025) Gan-Mai-Da-Zao Decoction Ameliorates Depressive-Like Behaviors in CUMS Mice via the Microbiota-Metabolism-Inflammation Axis. Phytomedicine, 145, Article 157018. [Google Scholar] [CrossRef] [PubMed]
[62] Fan, Q., Liu, Y., Sheng, L., Lv, S., Yang, L., Zhang, Z., et al. (2023) Chaihu-Shugan-San Inhibits Neuroinflammation in the Treatment of Post-Stroke Depression through the JAK/STAT3-GSK3β/PTEN/Akt Pathway. Biomedicine & Pharmacotherapy, 160, Article 114385. [Google Scholar] [CrossRef] [PubMed]
[63] Qu, S., Liu, M., Cao, C., Wei, C., Meng, X., Lou, Q., et al. (2021) Chinese Medicine Formula Kai-Xin-San Ameliorates Neuronal Inflammation of CUMs-Induced Depression-Like Mice and Reduces the Expressions of Inflammatory Factors via Inhibiting TLR4/IKK/NF-κB Pathways on BV2 Cells. Frontiers in Pharmacology, 12, Article 626949. [Google Scholar] [CrossRef] [PubMed]
[64] Sun, Q., Hu, M., Yuan, C., Ren, B., Zhong, M., Zhou, S., et al. (2024) Astragaloside IV Ameliorates Indomethacin-Induced Intestinal Inflammation in Rats through Inhibiting the Activation of NLRP3 Inflammasome. International Immunopharmacology, 135, Article 112281. [Google Scholar] [CrossRef] [PubMed]
[65] Paik, S., Kim, J.K., Silwal, P., Sasakawa, C. and Jo, E. (2021) An Update on the Regulatory Mechanisms of NLRP3 Inflammasome Activation. Cellular & Molecular Immunology, 18, 1141-1160. [Google Scholar] [CrossRef] [PubMed]
[66] 江克明. 郁证辨治[J]. 开卷有益(求医问药), 1997(11): 6-7.
[67] 张静研, 封继宏. 从自噬理论探讨扶正祛邪疗法作用机制思路初探[J]. 辽宁中医药大学学报, 2018, 20(10): 96-99.
[68] 郑清炼, 楚世峰, 许鑫, 陈乃宏. 黄芪甲苷的神经保护作用研究进展[J]. 中国药理学与毒理学杂志, 2019, 33(10): 877.
[69] 蒋晴, 罗煜, 朱正文, 梁雨生, 等. 基于中效方程的黄芩苷与小檗碱抗炎协同作用研究[J]. 中国药理学通报, 2020, 36(3): 443-444.
[70] Li, C., Huang, B. and Zhang, Y. (2021) Chinese Herbal Medicine for the Treatment of Depression: Effects on the Neuroendocrine-Immune Network. Pharmaceuticals, 14, Article 65. [Google Scholar] [CrossRef] [PubMed]
[71] Yu, J., Guo, M., Li, Y., Zhang, H., Chai, Z., Wang, Q., et al. (2019) Astragaloside IV Protects Neurons from Microglia-Mediated Cell Damage through Promoting Microglia Polarization. Folia Neuropathologica, 57, 170-181. [Google Scholar] [CrossRef] [PubMed]
[72] 员晨, 高昌俊. 肿瘤术后患者焦虑抑郁风险因素及干预研究进展[J]. 空军军医大学学报, 2025, 46(7): 974-980.
[73] Wang, Y., Deng, T., Liu, X., Fang, X., Mo, Y., Xie, N., et al. (2024) Smart Nanoplatforms Responding to the Tumor Microenvironment for Precise Drug Delivery in Cancer Therapy. International Journal of Nanomedicine, 19, 6253-6277. [Google Scholar] [CrossRef] [PubMed]
[74] 刘艳红, 周建平, 霍美蓉. 肿瘤微环境响应型智能纳米药物载体的研究进展[J]. 中国药科大学学报, 2016, 47(2): 125-133.
[75] Velapure, P.D., Chakote, S.R., Kansal, D., Barooah, A., Pawde, D.M. and Bobade, C.D. (2025) pH-Responsive Natural Polymers as Versatile Carriers for Drug Delivery in Breast Cancer: A Review. Biomedical Materials & Devices, 4, 3030-3050. [Google Scholar] [CrossRef
[76] Araki, R., Kita, A. and Yabe, T. (2024) Decreased Brain Ph Underlies Behavioral and Brain Abnormalities Induced by Chronic Exposure to Glucocorticoids in Mice. Biological and Pharmaceutical Bulletin, 47, 1836-1845. [Google Scholar] [CrossRef] [PubMed]
[77] Hagihara, H. and Miyakawa, T. (2025) Brain pH Is Decreased in Patients with Major Depressive Disorder: A Meta-Analysis of Postmortem Studies. International Journal of Neuropsychopharmacology, 28, i329. [Google Scholar] [CrossRef
[78] Rappeneau, V., Wilmes, L. and Touma, C. (2020) Molecular Correlates of Mitochondrial Dysfunctions in Major Depression: Evidence from Clinical and Rodent Studies. Molecular and Cellular Neuroscience, 109, Article 103555. [Google Scholar] [CrossRef] [PubMed]
[79] Bradley, K.A.L., Mao, X., Case, J.A.C., Kang, G., Shungu, D.C. and Gabbay, V. (2016) Increased Ventricular Cerebrospinal Fluid Lactate in Depressed Adolescents. European Psychiatry, 32, 1-8. [Google Scholar] [CrossRef] [PubMed]
[80] Tóth, O.M., Menyhárt, Á., Frank, R., Hantosi, D., Farkas, E. and Bari, F. (2020) Tissue Acidosis Associated with Ischemic Stroke to Guide Neuroprotective Drug Delivery. Biology, 9, Article 460. [Google Scholar] [CrossRef] [PubMed]
[81] Guo, K., Cao, D., Marchese-Thomas, L.P. and Dong, Y. (2025) Antibody Engineering for Receptor-Mediated Transcytosis across the Blood-Brain Barrier. Bioconjugate Chemistry, 36, 2109-2115. [Google Scholar] [CrossRef
[82] Ohtsuki, S. (2024) Insulin Receptor at the Blood-Brain Barrier: Transport and Signaling. Vitamins and Hormones, 126, 113-124.
[83] Ranjitha, V.R., Kumar, A. and Kaalappa, P. (2025) Bionanoconjugates in Neurodegeneration: Peptide-Nanoparticle Alliances for Next-Generation Therapies. Pharmaceutical Research, 42, 2379-2404. [Google Scholar] [CrossRef
[84] 杨子玉. N-半乳糖-O-组胺酰化羧甲基壳聚糖纳米粒的制备与性能研究[D]: [硕士学位论文]. 武汉: 武汉理工大学, 2010.
[85] 张银树. 刺玫果总黄酮纳米粒子的制备及性质表征[D]: [硕士学位论文]. 长春: 吉林大学, 2022.
[86] Wan, G.W., Xie, H., Mao, C.Q., Tang, R.Q., Yao, C. and Wang, Z. (2016) Difference in Inclusion Behavior of β-Cyclodextrin and Hydroxypropyl-β-Cyclodextrin with Menthol. China Journal of Chinese Materia Medica, 41, 3336-3341.
[87] 冯晓姣, 王继林, 杨文卓, 等. 中药多成分的共递送给药系统的构建策略和方法[J]. 中国实验方剂学杂志, 2024, 30(5): 186-196.
[88] 赵军宁, 陈春英, 华桦, 等. 中药复杂性原理新诠释: 方剂纳米体(FDN)作为中药药效物质的理想形式可实现对疾病动态网络多层次靶向调控[J]. 中国中药杂志, 2025, 50(19): 5305-5322.
[89] 文静, 牛俊淞, 吴玉珍, 邓婕, 李楠. 冰片-薄荷脑低共熔物载川芎嗪纳米乳凝胶制备[J]. 中成药, 2025, 47(8): 2522-2529.