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经鼻吸入川芎油调控BDNF/TrkB/CREB通路及重塑肠道微生态的抗抑郁作用机制

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中草药 | 药理与临床 2026,57(10): 3792-3806

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中草药 |药理与临床 2026 , 57 (10) : 3792 -3806

经鼻吸入川芎油调控BDNF/TrkB/CREB通路及重塑肠道微生态的抗抑郁作用机制

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刘昊林¹, 吴欠欠¹, 凌霞¹, 程楠¹, 李丹¹, 胡月¹, 龙宇¹, 甘青霞¹, 李楠¹

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通讯作者:

甘青霞

作者简介:

刘昊林: 刘昊林(2000—),男,硕士研究生,从事中药新剂型研究。E-mail:1918459136@qq.com

Antidepressant mechanism of nasal inhalation of Chuanxiong Rhizoma oil in modulating BDNF/TrkB/CREB pathway and remodelling gut microbiota

LIU Haolin, WU Qianqian, LING Xia, CHENG Nan, LI Dan, HU Yue, LONG Yu, GAN Qingxia, LI Nan

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doi: 10.7501/j.issn.0253-2670.2026.10.011

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目的探究川芎油经鼻吸入给药后对慢性不可预知温和应激（chronic unpredictable mild stress，CUMS）抑郁小鼠的影响及作用机制。方法通过气相色谱-质谱（gas chromatography-mass spectrometry，GC-MS）鉴定川芎油主要成分；构建小鼠CUMS抑郁模型，给予药物干预后，采用行为学实验、苏木素-伊红（hematoxylin-eosin，HE）及尼氏染色评价川芎油的药效作用；采用ELISA、Western blotting、qRT-PCR及16S rRNA进行机制研究。结果通过GC-MS鉴定川芎油的主要成分为Z-藁本内酯和洋川芎内酯A。经鼻吸入川芎油能显著改善CUMS小鼠的抑郁样行为（P＜0.05、0.01），减轻海马神经元损伤，上调海马组织脑源性神经营养因子（brain-derived neurotrophic factor，BDNF）/原肌球蛋白受体激酶B（tyrosine receptor kinase B，TrkB）/环磷腺苷效应元件结合蛋白（cAMP-response element binding protein，CREB）信号通路相关蛋白表达（P＜0.05、0.01），升高5-羟色胺（5-hydroxytryptamine，5-HT）、去甲肾上腺素（norepinephrine，NE）等单胺类神经递质水平（P＜0.05、0.01），抑制下丘脑-垂体-肾上腺（hypothalamic-pituitary-adrenal，HPA）轴的亢进（P＜0.05、0.01），抑制结肠组织中肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）等促炎因子水平（P＜0.05、0.01），增强屏障功能（P＜0.05、0.01），显著改善CUMS诱导的肠道微生物失调。CREB特异性抑制剂666-15显著逆转川芎油的抗抑郁作用（P＜0.01）。结论经鼻吸入川芎油通过BDNF/TrkB/CREB通路改善肠道功能障碍，从而治疗抑郁。

关键词

抑郁症 / 川芎油 / 抗炎 / 下丘脑-垂体-肾上腺轴 / 肠道菌群 / BDNF/TrkB/CREB通路 / Z-藁本内酯 / 洋川芎内酯A

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Objective To investigate the effect and mechanism of Chuanxiong (Chuanxiong Rhizoma) oil inhalation via nasal administration on chronic unpredictable mild stress (CUMS)-induced depressive mice. Methods The main components of Chuanxiong Rhizoma oil were identified by gas chromatography-mass spectrometry (GC-MS). A CUMS-induced depressive mouse model was established, and after drug intervention, the pharmacological effects of Chuanxiong Rhizoma oil were evaluated through behavioral tests, hematoxylin-eosin (HE) staining and Nissl staining. Mechanistic studies were conducted using ELISA, Western blotting, qRT-PCR and 16S rRNA. Results GC-MS identified Z-ligustilide and senkyunolide A as the primary components of Chuanxiong Rhizoma oil. Nasal inhalation of Chuanxiong Rhizoma oil significantly alleviated depressive-like behaviors in CUMS mice (P < 0.05, 0.01), reduced hippocampal neuronal damage, upregulated the expressions of brain-derived neurotrophic factor (BDNF)/tyrosine receptor kinase B (TrkB)/cAMP-response element binding protein (CREB) signaling pathway related proteins in hippocampus (P < 0.05, 0.01), elevated levels of monoamine neurotransmitters such as 5-hydroxytryptamine (5-HT) and norepinephrine (NE) (P < 0.05, 0.01), inhibited the hyperactivity of hypothalamic-pituitary-adrenal (HPA) axis (P < 0.05, 0.01), suppressed pro-inflammatory factors such as tumor necrosis factor-α (TNF-α) in colon tissue (P < 0.05, 0.01), enhanced barrier function (P < 0.05, 0.01), and significantly ameliorated CUMS-induced gut microbiota dysbiosis. The CREB-specific inhibitor 666-15 significantly reversed the antidepressant effects of Chuanxiong Rhizoma oil (P < 0.01). Conclusion Nasal inhalation of Chuanxiong Rhizoma oil alleviates depression by improving gut dysfunction through BDNF/TrkB/CREB pathway.

Key words

depression / Chuanxiong Rhizoma oil / anti-inflammation / hypothalamic-pituitary-adrenal axis / gut microbiota / BDNF/TrkB/CREB pathway / Z-ligustilide / senkyunolide A

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刘昊林, 吴欠欠, 凌霞, 程楠, 李丹, 胡月, 龙宇, 甘青霞, 李楠. 经鼻吸入川芎油调控BDNF/TrkB/CREB通路及重塑肠道微生态的抗抑郁作用机制. 中草药, 2026 , 57 (10) : 3792 -3806 . DOI: 10.7501/j.issn.0253-2670.2026.10.011

LIU Haolin, WU Qianqian, LING Xia, CHENG Nan, LI Dan, HU Yue, LONG Yu, GAN Qingxia, LI Nan. Antidepressant mechanism of nasal inhalation of Chuanxiong Rhizoma oil in modulating BDNF/TrkB/CREB pathway and remodelling gut microbiota[J]. Chinese Traditional and Herbal Drugs, 2026 , 57 (10) : 3792 -3806 . DOI: 10.7501/j.issn.0253-2670.2026.10.011

基金

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国家自然科学基金资助项目 (82474220); 成都中医药大学“杏林学者”学科人才科研提升计划 (QJJJ2022014); 四川省中医药科技产业创新团队专项 (2022C005)

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2026年第57卷第10期

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doi: 10.7501/j.issn.0253-2670.2026.10.011

接收时间：2025-11-18
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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