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交泰丸和5-羟色胺再摄取抑制剂治疗对抑郁症患者短链脂肪酸、神经炎症标志物及神经营养因子调节作用的临床研究

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中草药 | 药理与临床 2026,57(2): 574-582

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中草药 |药理与临床 2026 , 57 (2) : 574 -582

交泰丸和5-羟色胺再摄取抑制剂治疗对抑郁症患者短链脂肪酸、神经炎症标志物及神经营养因子调节作用的临床研究

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杨彤¹, 何媛媛¹, 黄梦楠², 李宇婷¹, 高杉¹, 于春泉¹

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通讯作者:

高杉

作者简介:

杨彤: 杨彤，博士研究生，研究方向为心血管疾病及心身疾病中医临床研究。E-mail: yangtuott@163.com

Clinical study on regulatory effects of Jiaotai Wan and selective serotonin reuptake inhibitors on short-chain fatty acids, neuroinflammatory markers, and neurotrophic factors in depressed patients

YANG Tong, HE Yuanyuan, HUANG Mengnan, LI Yuting, GAO Shan, YU Chunquan

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doi: 10.7501/j.issn.0253-2670.2026.02.017

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目的评价交泰丸和选择性5-羟色胺再摄取抑制剂（selective serotonin reuptake inhibitors，SSRIs）治疗抑郁症患者的临床疗效，并探讨其作用机制。方法基于前期的多中心、随机、阳性药平行对照临床试验生物样本数据，将纳入的83例抑郁症患者被分为交泰丸组（n＝25）、交泰丸联合SSRIs组（n＝29）和SSRIs组（n＝29）。采用混合线性模型分析各组治疗前后短链脂肪酸（short-chain fatty acids，SCFAs）、神经炎症标志物［环氧合酶-2（cyclooxygenase-2，COX-2）、前列腺素E₂（prostaglandin E₂，PGE₂）］及脑源性神经营养因子（brain derived neurotrophic factor，BDNF）的变化；通过Spearman相关性与结构方程模型探索治疗后生物标志物与临床症状［汉密尔顿抑郁量表（Hamilton depression rating scale，HAMD）评分］的关联及中介路径。结果 3组患者HAMD评分均较基线显著下降（P＜0.001），但组间无统计学差异。交泰丸组表现出丁酸水平的显著升高（P＝0.002）并维持较高乙酸、丙酸水平；SSRIs组异戊酸、异丁酸、己酸水平升高；交泰丸联合SSRIs组治疗后异丁酸、异戊酸和异己酸水平均显著提升，乙酸水平显著下降；交泰丸联合SSRIs组治疗后BDNF水平显著高于其他两组（P＜0.05）。相关性分析显示，治疗后交泰丸联合SSRIs组的PGE₂与BDNF呈强正相关（r＝0.609，P＜0.001），SSRIs组的COX-2与HAMD评分呈正相关（r＝0.451，P＝0.014），交泰丸组的异己酸与BDNF呈正相关（r＝0.445，P＝0.026）。中介分析提示，在交泰丸联合SSRIs组中，PGE₂通过BDNF影响HAMD评分的间接效应＝−0.065，P＝0.093。结论交泰丸、SSRIs单独治疗及交泰丸联合SSRIs治疗均能有效缓解抑郁症状，但在调节肠道SCFAs谱、神经炎症及神经营养因子方面表现出不同的作用模式。交泰丸联合SSRIs治疗可能通过调节支链脂肪酸代谢，并促进PGE₂与BDNF之间的正向关联，形成了潜在的有别于单一疗法的作用路径。这些发现为理解不同抗抑郁策略的差异化机制提供了初步证据，提示个性化治疗需考虑患者特定的生物学特征。

关键词

抑郁症 / 交泰丸 / 选择性5-羟色胺再摄取抑制剂 / 短链脂肪酸 / 神经炎症 / 脑源性神经营养因子 / 环氧合酶-2 / 前列腺素E₂ / 差异化调节 / 中介分析

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Objective To investigate clinical efficacy of Jiaotai Wan (JTW, 交泰丸), and selective serotonin reuptake inhibitors (SSRIs) in patients with depression, and to explore their underlying mechanisms. Methods Based on biological sample data from a previous multicenter, randomized, active-controlled parallel clinical trial, a total of 83 depression patients were divided into three groups: JTW group (n = 25), JTW combined with SSRIs group (n = 29), and SSRIs alone group (n = 29). A mixed linear model was used to analyze changes in short-chain fatty acids (SCFAs), neuroinflammatory markers [cyclooxygenase-2 (COX-2), prostaglandin E₂ (PGE₂)] and brain-derived neurotrophic factor (BDNF) before and after treatment in each group. Spearman correlation and structural equation modeling were used to explore the relationships between post-treatment biomarkers and clinical symptoms [Hamilton depression rating scale (HAMD) scores], and potential mediating pathways. Results HAMD scores decreased significantly from baseline in all three groups (P < 0.001), but there was no significant differences between the groups. The JTW group showed a significant increase in butyrate levels (P = 0.002) and maintained higher levels of acetate and propionate. The SSRIs group was associated with increased levels of isovalerate, isobutyrate, and hexanoate. After treatment, the JTW + SSRIs group showed significant increases in isobutyrate, isovalerate, and isohexanoate levels, and a significant decrease in acetate levels. The combined group had significantly higher BDNF levels than the other two groups (P < 0.05). The PGE₂ levels in the combined group were also higher than in the JTW group both at baseline and after treatment (P < 0.05). Correlation analysis showed a strong positive correlation between PGE₂ and BDNF in the combined group after treatment (r = 0.609, P < 0.001). In the SSRIs group, COX-2 was positively correlated with HAMD score (r = 0.451, P = 0.014). In the JTW group, isohexanoate was positively correlated with BDNF (r = 0.445, P = 0.026). Mediation analysis suggested a potential indirect effect in the combined group, where PGE₂ influenced HAMD scores through BDNF (indirect effect = −0.065, P = 0.093). Conclusion JTW alone, SSRIs alone and JTW combined with SSRIs all can effectively alleviate depressive symptoms. However, they showed different patterns in regulating gut SCFAs, neuroinflammation, and neurotrophic factors. JTW combined with SSRIs may modulate branched-chain fatty acid metabolism and promote a positive association between PGE₂ and BDNF, thereby creating a distinct pathway that differs from single therapies. These findings provide preliminary evidence for understanding the differential mechanisms of various antidepressant strategies, suggesting that personalized treatment should consider patients’ specific biological characteristics.

Key words

depression / Jiaotai Wan / selective serotonin reuptake inhibitors / short-chain fatty acids / neuroinflammation / brain-derived neurotrophic factor / cyclooxygenase-2 / prostaglandin E₂ / differential regulation / mediation analysis

引用本文

杨彤, 何媛媛, 黄梦楠, 李宇婷, 高杉, 于春泉. 交泰丸和5-羟色胺再摄取抑制剂治疗对抑郁症患者短链脂肪酸、神经炎症标志物及神经营养因子调节作用的临床研究. 中草药, 2026 , 57 (2) : 574 -582 . DOI: 10.7501/j.issn.0253-2670.2026.02.017

YANG Tong, HE Yuanyuan, HUANG Mengnan, LI Yuting, GAO Shan, YU Chunquan. Clinical study on regulatory effects of Jiaotai Wan and selective serotonin reuptake inhibitors on short-chain fatty acids, neuroinflammatory markers, and neurotrophic factors in depressed patients[J]. Chinese Traditional and Herbal Drugs, 2026 , 57 (2) : 574 -582 . DOI: 10.7501/j.issn.0253-2670.2026.02.017

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国家自然科学基金面上项目 (82074220)

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吕志远, 曹玲玲, 游佩进, 等. 天然多糖通过微生物-肠-脑轴缓解抑郁症的作用机制与治疗潜力[J]. 中草药, 2025, 56(19):7222-7236.
吴梅, 阮彬彬, 李天平. 选择性5-羟色胺再摄取抑制剂(SSRIs)类抗抑郁药的快速评价[J]. 药物评价研究, 2025, 48(4):952-963.
Marks S. A clinical review of antidepressants, their sexual side-effects, post-SSRI sexual dysfunction, and serotonin syndrome[J]. Br J Nurs, 2023, 32(14):678-682.
Agirman G, Yu K B, Hsiao E Y. Signaling inflammation across the gut-brain axis[J]. Science, 2021, 374(6571):1087-1092.
Młynarska E, Gadzinowska J, Tokarek J, et al. The role of the microbiome-brain-gut axis in the pathogenesis of depressive disorder[J]. Nutrients, 2022, 14(9):1921.
Chen Q, Luo Y, Kuang S N, et al. Cyclooxygenase-2 signalling pathway in the cortex is involved in the pathophysiological mechanisms in the rat model of depression[J]. Sci Rep, 2017, 7(1):488.
Zhang J C, Yao W, Hashimoto K. Brain-derived neurotrophic factor (BDNF)-TrkB signaling in inflammation-related depression and potential therapeutic targets[J]. Curr Neuropharmacol, 2016, 14(7):721-731.
汪冉, 张忠晶, 曹定雯, 等. 交泰丸调节脑源性神经营养因子改善老年心肾不交型脑梗死患者抑郁和睡眠障碍的临床研究[J]. 微循环学杂志, 2021, 31(4):22-26.
陈佩瑶, 戴国梁, 王艳军, 等. 交泰丸入脑成分通过PTEN/AKT/NF-κB通路抑制LPS诱导BV2细胞炎症的机制研究[J]. 中国医院药学杂志, 2025, 45(6):614-621.
Huang M N, He Y Y, Yang T, et al. Jiaotaiwan activates serum SCFAs and upregulates cAMP-PKA-CREB-BDNF signaling pathway for antidepressant effects:A multicenter, randomized, controlled study[J]. Chin Herb Med, 2025, 17(4):790-797.
黄梦楠, 何媛媛, 杨彤, 等. 交泰丸治疗抑郁症心肾不交证患者的中医证候疗效及对COX2/PGE₂信号通路的影响[J]. 天津中医药, 2025, 42(1):15-19.
中华中医药学会. 中医内科常见疾病诊疗指南·西医病证部分[M]. 北京:中国中医药出版社, 2008:294-296.
Nöbbelin L, Bogren M, Mattisson C, et al. Incidence of melancholic depression by age of onset and gender in the Lundby population, 1947-1997[J]. Eur Arch Psychiatry Clin Neurosci, 2023, 273(5):1163-1173.
Malmir H, Mirzababaei A, Moradi S, et al. Metabolically healthy status and BMI in relation to depression:A systematic review of observational studies[J]. Diabetes Metab Syndr, 2019, 13(2):1099-1103.
Ofori M A, Mensah D K, Nizeyimana I, et al. High blood pressure and depression among the working population of Ghana:A generalized linear model of the risk factors[J]. Depress Anxiety, 2024, 2024(1):5261760.
Stilling R M, van de Wouw M, Clarke G, et al. The neuropharmacology of butyrate:The bread and butter of the microbiota-gut-brain axis?[J]. Neurochem Int, 2016, 99:110-132.
Li Y T, Liu A F, Chen K J, et al. Sodium butyrate alleviates lead-induced neuroinflammation and improves cognitive and memory impairment through the ACSS2/H3K9ac/BDNF pathway[J]. Environ Int, 2024, 184:108479.
Ichimura-Shimizu M, Kurrey K, Miyata M, et al. Emerging insights into the role of BDNF on health and disease in periphery[J]. Biomolecules, 2024, 14(4):444.
Tikhonova M A, Zhanaeva S Y, Shvaikovskaya A A, et al. Neurospecific molecules measured in periphery in humans:How do they correlate with the brain levels? A systematic review[J]. Int J Mol Sci, 2022, 23(16):9193.
Kishi T, Yoshimura R, Ikuta T, et al. Brain-derived neurotrophic factor and major depressive disorder:Evidence from meta-analyses[J]. Front Psychiatry, 2017, 8:308.
Puhlmann L C, Linz R, Valk S L, et al. Association between hippocampal structure and serum brain-derived neurotrophic factor (BDNF) in healthy adults:A registered report[J]. Neuroimage, 2021, 236:118011.
Skonieczna-Żydecka K, Grochans E, Maciejewska D, et al. Faecal short chain fatty acids profile is changed in Polish depressive women[J]. Nutrients, 2018, 10(12):1939.
Golia M T, Poggini S, Alboni S, et al. Interplay between inflammation and neural plasticity:Both immune activation and suppression impair LTP and BDNF expression[J]. Brain Behav Immun, 2019, 81:484-494.
Mehdi S, Wani S U D, Krishna K L, et al. A review on linking stress, depression, and insulin resistance via low-grade chronic inflammation[J]. Biochem Biophys Rep, 2023, 36:101571.
Hutchinson A J, Chou C L, Israel D D, et al. Activation of EP2 prostanoid receptors in human glial cell lines stimulates the secretion of BDNF[J]. Neurochem Int, 2009, 54(7):439-446.

2026年第57卷第2期

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doi: 10.7501/j.issn.0253-2670.2026.02.017

接收时间：2025-11-21
首发时间：2026-09-09

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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