中医药学报

栀子豉汤通过调节KYNA/QA平衡与小胶质细胞极化改善CUMS大鼠抑郁样行为的研究

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孟拓 , 秦铭骏

中医药学报 | 实验研究 2026,54(9): 7-18

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中医药学报 |实验研究 2026 , 54 (9) : 7 -18

栀子豉汤通过调节KYNA/QA平衡与小胶质细胞极化改善CUMS大鼠抑郁样行为的研究

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孟拓, 秦铭骏

作者信息

黑龙江中医药大学，黑龙江哈尔滨 150040

作者简介:

孟拓（1989-），男，博士，讲师，研究方向：方剂配伍规律研究。

Study on the Improvement of Depression-Like Behavior in CUMS Rats by Zhizi Chi Decoction Through Regulating KYNA/QA Balance and Microglial Polarization

Tuo MENG, Mingjun QIN

Affiliations

Heilongjiang University of Chinese Medicine, Harbin 150040, China

出版时间: 2026-09-20 doi: 10.19664/j.cnki.1002-2392.260173

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摘要

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目的：

探讨栀子豉汤（ZZCD）对慢性不可预测性应激（CUMS）诱导大鼠抑郁样行为的作用及机制。

方法：

大鼠随机分为5组，①对照组（Control）：不接受慢性不可预测性轻度应激（CUMS）及药物处理；②ZZCD组：未接受CUMS，对应给药时间点灌胃栀子豉汤（ZZCD，10 g·kg^-1·d^-1）；③CUMS组：连续7周接受CUMS处理；④CUMS+氟西汀组（CUMS + Flu）：接受7周CUMS，自第21天起灌胃氟西汀（fluoxetine，10 mg·kg^-1 ·d^-1）连续4周；⑤CUMS + ZZCD组：接受7周CUMS，自第21天起灌胃ZZCD （10 g·kg^-1 ·d^-1）连续4周。小胶质细胞系BV-2在对数生长期进行分组并处理，①对照组（Control）：不加任何处理；②ZZCD组：加入ZZCD 4 mg/mL处理24 h；③QA组：加入喹啉酸（QA，5 mmol/L）处理24 h；④QA + ZZCD组：同时加入QA（5 mmol/L）与ZZCD（4 mg/mL）处理24 h。采用蔗糖偏好实验（SPT）、旷场实验（OFT）、高架十字迷宫实验（EPM）评价大鼠行为学；采用免疫荧光、实时定量聚合酶链式反应（qRT-PCR）、蛋白质印迹（Western blot）技术检测小胶质细胞活化和炎症因子水平；酶联免疫吸附试验（ELISA）及生化试剂盒测定犬尿氨酸（KYNA）、喹啉酸（QA）及氧化应激指标水平；并在小胶质细胞BV-2中进行QA处理验证。同时采用液相色谱-质谱（LC-MS）对栀子豉汤进行化学成分分析，以表征其物质基础特征。

结果：

ZZCD改善CUMS大鼠抑郁和焦虑样行为，抑制M1型活化并促进M2型极化（P < 0.001），纠正KYNA/QA失衡，降低活性氧（ROS）和丙二醛（MDA）（P < 0.001），提高超氧化物歧化酶（SOD）和过氧化氢酶（CAT）活性（P < 0.01，P < 0.001），抑制核因子-κB（NF-κB）通路并激活ERK/CREB信号（P < 0.001），同时上调海马脑源性神经营养因子（BDNF）及突触可塑性相关蛋白突触后致密物质95（PSD95）和突触素（SYP）的表达（P < 0.001）。

结论：

栀子豉汤可通过多靶点作用改善CUMS大鼠抑郁样行为，其机制可能与抑制神经炎症、调控犬尿氨酸通路、减轻氧化应激并促进神经可塑性恢复有关，为中药抗抑郁提供实验依据。

关键词

栀子豉汤 / 抑郁症 / 小胶质细胞 / 犬尿氨酸通路 / NF-κB / ERK-CREB / 神经可塑性

Abstract

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To investigate the antidepressant effects of Zhizi Chi Decoction (ZZCD) on depression-like behaviors induced by chronic unpredictable mild stress (CUMS) in rats and to elucidate the underlying mechanisms.

Methods:

Depression- and anxiety- like behaviors were evaluated using the sucrose preference test (SPT), open field test (OFT), and elevated plus maze (EPM). Microglial activation and inflammatory mediators were assessed by immunofluorescence, quantitative real-time PCR (qRT-PCR), and Western blot. Levels of kynurenic acid (KYNA), quinolinic acid (QA), and oxidative stress markers were measured using enzyme-linked immunosorbent assay (ELISA) and biochemical kits. In addition, QA-treated BV-2 microglial cells were employed to validate the cellular mechanisms. Liquid chromatography-mass spectrometry (LC-MS) analysis was performed to characterize the chemical profile of ZZCD.

Results:

ZZCD significantly improved depression- and anxiety- like behaviors in CUMS rats, suppressed M1-type activation and promoted M2 polarization of microglia, corrected the imbalance of KYNA/QA, and alleviated oxidative stress by reducing reactive oxygen species (ROS) and malondialdehyde (MDA) while enhancing superoxide dismutase (SOD) and catalase (CAT) activities. Moreover, ZZCD inhibited the NF-κB pathway and activated ERK/CREB signaling in both hippocampal tissues and BV-2 cells, accompanied by upregulation of brain-derived neurotrophic factor (BDNF) and synaptic plasticity-related proteins, including postsynaptic density protein 95 (PSD95) and synaptophysin.

Conclusion:

ZZCD exerts antidepressant effects through multi-target mechanisms, including regulation of microglial activation, kynurenine pathway balance, oxidative stress reduction, and ERK/CREB pathway activation, which may contribute to the restoration of synaptic plasticity. These findings provide experimental evidence supporting the potential of ZZCD as a traditional Chinese medicine-based intervention for depression.

Key words

Zhizi Chi Decoction / Depression / Microglia / Kynurenine pathway / NF-κB / ERK/CREB / Synaptic plasticity

引用本文

孟拓, 秦铭骏. 栀子豉汤通过调节KYNA/QA平衡与小胶质细胞极化改善CUMS大鼠抑郁样行为的研究. 中医药学报, 2026 , 54 (9) : 7 -18 . DOI: 10.19664/j.cnki.1002-2392.260173

Tuo MENG, Mingjun QIN. Study on the Improvement of Depression-Like Behavior in CUMS Rats by Zhizi Chi Decoction Through Regulating KYNA/QA Balance and Microglial Polarization[J]. Acta Chinese Medicine and Pharmacology, 2026 , 54 (9) : 7 -18 . DOI: 10.19664/j.cnki.1002-2392.260173

基金

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黑龙江省中医药管理局国医大师学术思想传承科研课题(GY2022-03)

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2026年第54卷第9期

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文章信息

doi: 10.19664/j.cnki.1002-2392.260173

接收时间：2025-08-28
首发时间：2026-09-11
出版时间：2026-09-20

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收稿日期：2025-08-28
修回日期：2026-06-03

基金

黑龙江省中医药管理局国医大师学术思想传承科研课题(GY2022-03)

作者信息

黑龙江中医药大学，黑龙江哈尔滨 150040

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https://castjournals.cast.org.cn/joweb/zyyxb/CN/10.19664/j.cnki.1002-2392.260173

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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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