中医药信息2025，Vol.42Issue(8)：1-8,15,9.DOI:10.19656/j.cnki.1002-2406.20250801
基于ERK/CREB/BDNF通路探讨百合地黄汤抗抑郁的作用机制
Mechanism of Baihe Dihuang Decoction in Anti-depressant via ERK/CREB/BDNF Pathway
摘要
Abstract
Objective:To investigate the ameliorative effects of Baihe Dihuang Decoction(BDD)on depressive model mice and its regulatory mechanism on extracellular signal-regulated protein kinase(ERK)/cyclic AMP response element-binding protein(CREB)/brain-derived neurotrophic factor(BDNF)pathway.Methods:Sixty C57BL/6 mice were randomly divided into blank group,model group,fluoxetine group[2.5 mg/(kg·d)],high-dose BDD group[15.86 g/(kg·d)],medium-dose BDD group[7.83 g/(kg·d)],and low-dose BDD group[3.93 g/(kg·d)],with 10 mice in each group.Groups,except for the blank one,were subjected to chronic restraint stress(CRS)to establish depression models,with 4 weeks of continuous gavage administration.Behavioral changes were assessed using open field test and sucrose preference test.Cortical neuron morphology was observed via HE staining and Nissl staining.Immunohistochemistry was applied to detect cortical BDNF expression.ELISA was used to measure brain levels of 5-hydroxytryptamine(5-HT),dopamine(DA),norepinephrine(NE),corticosterone(CORT),and glucocorticoids including corticotropin-releasing hormone(CRH)and adrenocorticotropic hormone(ACTH).qPCR was utilized to analyze ERK,CREB,and BDNF levels in the brain.Western blot examined ERK,CREB,and BDNF protein expression in the brain.Results:Compared with the blank group,the model group showed significantly decreased sucrose preference index,central zone entries and duration in open field test(P<0.01),sparse/disordered cortical neurons,reduced Nissl bodies,decreased BDNF expression(P<0.01),reduced 5-HT,DA,NE levels(P<0.01),elevated CORT,CRH,ACTH levels(P<0.01),and downregulated ERK,CREB,BDNF mRNA,and protein(P<0.01).Compared with the model group,fluoxetine and all BDD dose groups exhibited increased sucrose preference index,central zone entries and duration(P<0.01,P<0.05),well-arranged cortical neurons,abundant Nissl bodies,elevated BDNF expression(P<0.01,P<0.05),significantly increased 5-HT,DA,NE(P<0.01,P<0.05),significantly decreased CORT,CRH and ACTH expression(P<0.01,P<0.05),and significantly increased ERK,CREB,BDNF mRNA and protein(P<0.01,P<0.05).Conclusion:BDD can regulate brain neurotransmitter secretion and improve depressive-like behaviors,and the mechanism may be related to the activation of ERK/CREB/BDNF pathway.关键词
抑郁症/百合地黄汤/神经递质/ERK/CREB/BDNF通路Key words
Depression/Baihe Dihuang Decoction/Neurotransmitters/ERK/CREB/BDNF signaling pathway引用本文复制引用
安富竹,乔明琦..基于ERK/CREB/BDNF通路探讨百合地黄汤抗抑郁的作用机制[J].中医药信息,2025,42(8):1-8,15,9.基金项目
国家重点基础研究发展规划项目(2011CB505102) （2011CB505102）
济南市"高校20条"资助项目(2020GXRC002) （2020GXRC002）
