栀子豉汤通过调节色氨酸代谢及脑源性神经营养因子信号改善大鼠抑郁样行为

doi:10.12122/j.issn.1673-4254.2026.04.17

南方医科大学学报 ›› 2026, Vol. 46 ›› Issue (4): 890-898.doi: 10.12122/j.issn.1673-4254.2026.04.17

栀子豉汤通过调节色氨酸代谢及脑源性神经营养因子信号改善大鼠抑郁样行为

孟拓¹(), 秦铭骏², 夏永刚³()

^1.黑龙江中医药大学，基础医学院方剂学教研室，黑龙江哈尔滨 150000
^2.黑龙江中医药大学，第二临床医学院，黑龙江哈尔滨 150000
^3.黑龙江中医药大学，药物安全性评价中心，黑龙江哈尔滨 150000

收稿日期:2025-06-24 出版日期:2026-04-20 发布日期:2026-04-24
通讯作者: 夏永刚 E-mail:13159801315@163.com;zhongyiboshimt@163.com
作者简介:孟拓，讲师，博士，E-mail: 13159801315@163.com
基金资助:
国家自然科学基金青年资助项目(82004245)

Zhizichi Decoction alleviates depression-like behaviors in rats exposed to chronic unpredictable mild stress by modulating tryptophan metabolism and the BDNF signaling pathway

Tuo MENG¹(), Mingjun QIN², Yonggang XIA³()

^1.Department of Formula Studies, School of Basic Medical Sciences, Heilongjiang University of Traditional Chinese Medicine, Harbin 150000, China
^2.Second Clinical Medical College, Heilongjiang University of Traditional Chinese Medicine, Harbin 150000, China
^3.Center for Drug Safety Evaluation, Heilongjiang University of Traditional Chinese Medicine, Harbin 150000, China

Received:2025-06-24 Online:2026-04-20 Published:2026-04-24
Contact: Yonggang XIA E-mail:13159801315@163.com;zhongyiboshimt@163.com
Supported by:
Youth Program of National Natural Science Foundation of China(82004245)

摘要/Abstract

摘要：

目的探讨栀子豉汤对慢性不可预见轻度应激（CUMS）大鼠抑郁症模型中色氨酸代谢途径、炎症相关信号通路和神经营养因子相关信号通路的调节作用，并评估其抗抑郁潜力。方法选用健康成年雄性SD大鼠建立CUMS模型，随机分为5组（n=10）：正常对照组、模型组、氟西汀组、栀子豉汤低剂量组和高剂量组。各组在建模后接受相应药物干预，持续4周。通过强迫游泳实验（FST）、悬尾实验（TST）、自愿活动记录、HE染色及组织损伤评分、Western blotting和ELISA检测，评估栀子豉汤对大鼠抑郁样行为、脑组织病理学、色氨酸（Trp）代谢、神经递质水平、炎症及脑源性神经营养因子（BDNF）相关通路的影响。结果与正常组相比，模型组不动时间延长，游泳和挣扎时间缩短（P<0.01）；与模型组相比，氟西汀组及栀子豉汤各剂量组均显著改善（P<0.01），高剂量组效果最显著（P<0.05）。HE染色显示，栀子豉汤降低脑组织损伤评分（P<0.01）。Western blotting显示，栀子豉汤上调TPH2并下调IDO、KMO、MAO-A（P<0.01），抑制NF-κB/NLRP3炎症通路并上调TrkB、p-CREB、p-AKT、p-ERK（P<0.01）。ELISA结果显示，栀子豉汤显著升高Trp、5-羟色胺、5-羟吲哚乙酸水平，降低犬尿氨酸及炎症因子肿瘤坏死因子（TNF-α）、白细胞介素-6（IL-6）、白细胞介素-1β（IL-1β）（P<0.01），并上调BDNF表达（P<0.01）。结论栀子豉汤通过调节色氨酸代谢途径、神经递质代谢（促进合成并减少分解）、炎症反应及BDNF信号通路，从而缓解CUMS大鼠的抑郁样行为和改善脑组织病理学损伤，具有潜在的抗抑郁作用。

关键词: 栀子豉汤, 抑郁症, 色氨酸代谢, 神经递质, 炎症信号通路, 神经营养因子

Abstract:

Objective To evaluate the regulatory effects of Zhizichi Decoction on tryptophan metabolism, inflammation, and neurotrophic factor-related signaling pathways and its potential antidepressant effects in a rat model of depression induced by chronic unpredictable mild stress (CUMS). Methods Adult male SD rat models of CUMS-induced depression were randomized into CUMS model group, fluoxetine group, low-dose Zhizichi Decoction group (LZZCD), and high-dose Zhizichi Decoction group (HZZCD) (n=10), with another 10 normal rats as the control group. After modeling, the rats received daily drug interventions via gavage for 4 weeks. Forced swimming test, tail suspension test, and voluntary activity recording were used to assess depressive-like behaviors of the rats. HE staining, Western blotting and ELISA were used to evaluate the changes in brain tissue pathologies, tryptophan metabolism, neurotransmitter levels, inflammation and brain-derived neurotrophic factor (BDNF)-related pathways of the rats. Results The rat models with CUMS showed significantly increased immobility and reduced swimming and struggling time. Both fluoxetine and Zhizichi Decoction at the two doses markedly alleviated depressive-like behaviors of the rat models, and high-dose Zhizichi Decoction produced the strongest ameliorating effect. Zhizichi Decoction treatment reduced brain injury scores of the rats, upregulated TPH2 and downregulated IDO, KMO, and MAO-A expressions in the hippocampus, causing also inhibition of the NF‑κB/NLRP3 pathway and increased hippocampal expressions of TrkB, p-CREB, p-AKT, and p-ERK. ELISA results demonstrated that Zhizichi Decoction treatment increased Trp, 5-HT, and 5-HIAA levels, decreased the levels of Kyn and inflammatory cytokines, and upregulated BDNF expression in the hippocampus of the rat models. Conclusion Zhizichi Decoction alleviates depressive-like behaviors and brain pathologies in CUMS rats by regulating tryptophan metabolism, enhancing synthesis and reducing degradation of neurotransmitters, inhibiting inflammatory response, and upregulating the BDNF signaling pathway.

Key words: Zhizichi Decoction, depression, tryptophan metabolism, neurotransmitters, inflammatory signaling pathway, neurotrophic factor

孟拓, 秦铭骏, 夏永刚. 栀子豉汤通过调节色氨酸代谢及脑源性神经营养因子信号改善大鼠抑郁样行为[J]. 南方医科大学学报, 2026, 46(4): 890-898.

Tuo MENG, Mingjun QIN, Yonggang XIA. Zhizichi Decoction alleviates depression-like behaviors in rats exposed to chronic unpredictable mild stress by modulating tryptophan metabolism and the BDNF signaling pathway[J]. Journal of Southern Medical University, 2026, 46(4): 890-898.

图/表 7

图1 　栀子豉汤对CUMS大鼠抑郁样行为的影响

Fig.1 Effects of Zhizichi Decoction on depressive-like behaviors in rats exposed to chronic unpredictable mild stress (CUMS). A: Immobility time and swimming time in forced swim test. B: Immobility time and struggling time in tail suspension test. C: Activity count and activity time recorded in voluntary activity monitoring. n=10, **P<0.01.

图2 HE染色及脑组织损伤评分结果

Fig.2 HE staining of the brain tissues of the rats(A) and brain injury scores (B). n=10, **P<0.01.

图3 栀子豉汤对CUMS大鼠海马组织中色氨酸代谢相关酶(TPH2、IDO、KMO)及神经递质降解相关酶(MAO-A)蛋白表达的影响

Fig.3 Effects of Zhizichi Decoction on expressions of tryptophan metabolism-related enzymes (TPH2, IDO, and KMO) and neurotransmitter degradation-related enzyme MAO-A in the hippocampal tissues of CUMS rats. n=10, **P<0.01.

图4 栀子豉汤对CUMS大鼠色氨酸代谢产物及神经递质水平的影响

Fig.4 Effects of Zhizichi Decoction on tryptophan metabolites and neurotransmitter levels in CUMS rats. A: Serum levels of tryptophan (Trp), kynurenine (Kyn), and 5-hydroxytryptamine (5-HT). B: Hippocampal levels of 5-HT and its primary metabolite 5-hydroxyindoleacetic acid (5-HIAA). n=10, **P<0.01.

图5 栀子豉汤对CUMS大鼠血清、海马和前额叶皮层中炎症因子水平的影响

Fig.5 Effects of Zhizichi Decoction on TNF-α (A), IL-6 (B), and IL-1β (C) levels in the serum, hippocampus, and prefrontal cortex of CUMS rats (Mean±SD).n=10, **P<0.01.

图6 栀子豉汤对CUMS大鼠脑组织NF-κB/NLRP3炎症信号通路相关蛋白表达的影响

Fig.6 Effects of Zhizichi Decoction on the expression of NF-κB/NLRP3 inflammatory signaling pathway proteins in the brains of CUMS rats. A: Western blot bands of NF‑κB p65, p-p65, IκBα, p-IκBα, NLRP3, and cleaved caspase-1. B: Quantitative analysis of relative protein expression (Mean±SD). n=3, **P<0.01.

图7 栀子豉汤对CUMS大鼠脑源性神经营养因子(BDNF)及其下游信号通路的影响

Fig.7 Effects of Zhizichi Decoction on BDNF and its downstream signaling pathways in CUMS rats. A: Levels of BDNF (n=10). B: Protein bands of TrkB, p-CREB, p-AKT, and p-ERK in Western blotting. C: Quantitative analysis of relative protein expression levels (n=3). **P<0.01.

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栀子豉汤通过调节色氨酸代谢及脑源性神经营养因子信号改善大鼠抑郁样行为

Zhizichi Decoction alleviates depression-like behaviors in rats exposed to chronic unpredictable mild stress by modulating tryptophan metabolism and the BDNF signaling pathway

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