时珍国医国药2025，Vol.36Issue(19)：3661-3669,9.DOI:10.70976/j.1008-0805.SZGYGY-2025-1909
乌梅丸调控BDNF/TrkB/PLCγ1途径改善突触可塑性缓解CUMS大鼠焦虑和抑郁样行为机制研究
Wumei Pill(乌梅丸)regulates the BDNF/TrkB/PLCγ1 pathway to alleviate synaptic plasticity and anxiety and depression-like behaviors in chronic unpredictable mild stress rats
摘要
Abstract
Objective To investigate the mechanism by which Wumei Pill(乌梅丸,WMP)ameliorates anxiety and depression-like behaviors in chronic unpredictable mild stress(CUMS)rats through regulation of the brain-derived neurotrophic factor(BDNF)/tyro-sine kinase receptor B(TrkB)/phospholipase Cγ1(PLCγ1)pathway and synaptic plasticity in the hippocampal dentate gyrus(DG).Methods Forty SPF male SD rats were randomly assigned to four groups(n=10 per group):the normal control,model,WMW(gavaged with Chinese medicine formula granule solution,2.27 g·kg-1·d-1),and fluoxetine(gavaged with fluoxetine hydrochloride solution,2.0 mg·kg-1·d-1).A depression model was established using the CUMS protocol.Behavioral tests(open field test,sucrose preference test,forced swimming test)were conducted before and after modeling.Pathological morphology of the hippocampal dentate gyrus(DG)was assessed using HE staining.The mRNA and protein expressions of synaptic markers,postsynaptic density protein 95(PSD95)and synaptophysin(SYP),were detected by RT-qPCR and immunohistochemistry(IHC),respectively.The protein expres-sions of key components in the BDNF/TrkB/PLCγ1 and calcium/calmodulin-dependent protein kinase Ⅱ(CaMKⅡ)/cAMP-response ele-ment binding protein(CREB)pathways were detected by Western blot(WB)and IHC.Results Following CUMS modeling,rats exhib-ited anxiety-and depression-like behaviors,neuronal damage in the DG,significantly decreased expressions of PSD95 and SYP(P<0.01),and suppressed BDNF/TrkB/PLCγ1 and CaMKⅡ/CREB pathway activity(P<0.01).After WMP intervention,these anxiety-and depression-like behaviors were alleviated,neuronal damage was ameliorated,expressions of PSD95 and SYP were significantly increased(P<0.01 or P<0.05),and the BDNF/TrkB/PLCγ1 and CaMKⅡ/CREB pathways were activated(P<0.01 or P<0.05).Conclusion WMP alleviates anxiety and depression-like behaviors in CUMS rats,potentially by enhancing synaptic plasticity in the hip-pocampal DG.This effect may be mediated through activation of the BDNF/TrkB/PLCγ1 pathway and its downstream CaMKⅡ/CREB sig-naling cascade.关键词
抑郁症/慢性心理应激/突触可塑性/脑源性神经营养因子/酪氨酸激酶受体B/磷脂酶Cγ1信号通路/乌梅丸Key words
Depressive disorder/Chronic unpredictable mild stress/Synaptic plasticity/BDNF/TrkB/PLCγ1 signaling path-way/Wumei Wan(乌梅丸)分类
医药卫生引用本文复制引用
王浩,王杰鹏,方朝义,方芳..乌梅丸调控BDNF/TrkB/PLCγ1途径改善突触可塑性缓解CUMS大鼠焦虑和抑郁样行为机制研究[J].时珍国医国药,2025,36(19):3661-3669,9.基金项目
河北省中医药类科研计划项目(2022030) （2022030）
国家级大学生创新创业计划训练项目(202214432005) （202214432005）
河北省大学生创新创业训练计划项目(S202314432011) （S202314432011）
