归脾汤对慢性束缚应激小鼠焦虑样行为的改善作用及机制OA

OBJECTIVE To observe the ameliorative effects of Guipi decoction(GP)on anxiety-like behaviors in a chronic restraint stress(CRS)mouse model and to explore its underlying mecha-nisms.METHODS The major chemical components of GP aqueous extract were identified by-ultra-per-formance liquid chromatography coupled with quadrupole-exactive Orbitrap mass spectrometry(UPLC-Q-Exactive Orbitrap MS).Male C57BL/6J mice were randomly divided into control group,model group,model+buspirone 5mg·kg-1 group,and model+GP 1.09,2.18 and 4.36g·kg-1 groups,with continuous intragastric administration for 16 days.Except for the control group,mice in other groups were subjected to the CRS procedure 1 hour after daily administration for 14 consecutive days.Anxiety-like behaviors were assessed using the open field test,elevated plus maze test(day15),and light-dark box test(day16).Pathological changes in hippocampal neurons were observed by HE staining and Golgistaining.The positive expressions of silent information regulator 1(SIRT1)and brain-derived neurotrophic factor(BDNF)were detected by immunohistochemistry.Western blotting was employed to measurethe expression levels of postsynaptic density protein 95(PSD95),SIRT1,BDNF,and tropomyosin receptor kinase B(TrkB),as well as the phosphorylation levels of extracellular signal-regulated kinase(ERK)and cAMP response element-binding protein(CREB).RESULTS Compared with control group,anxiety-like behaviors,neuronal damage,and synaptic plasticity-related proteins in model group were signifi-cantly reduced.Compared with model group,these behavioral and pathological abnormalities in groups treated with model+GP(2.18 and 4.36 g·kg-1)were significantly ameliorated.Furthermore,the expres-sion of PSD95,SIRT1,BDNF,TrkB,and the phosphorylation levels of ERK and CREB in model+GP2.18 g·kg-1 were significantly up-regulated.CONCLUSION Anxiety-like behaviors in CRS model mice were significantly ameliorated by GP,and its mechanism maybe associated with the improvement of synaptic plasticity via the SIRT1/CREB/BDNF signaling pathway.