Mechanism of Zishen Shugan Decoction(滋肾疏肝方)on Perimenopausal Depression Model Mice
Objective To explore the effect of Zishen Shugan Decoction(滋肾疏肝方,ZSD)on perimenopausal depressive dis-order(PDD)and the underlying molecular mechanism.Methods PDD mouse model was performed by ovariectomy and chronic unpredictable mild stress.Forty-eight mice were randomly divided into sham operation group,model group,ZSD low,medium,high concentration groups and positive control group,with 8 mice in each group.The ZSD low,medium,and high concentration groups were given ZSD with the corresponding concentration(0.38 g/mL,0.76 g/mL and 1.52 g/mL)by gavage,while the posi-tive control group was given 0.21 g/mL of fluoxetine hydrochloride and estradiol valerate suspension by gavage.It observed the behavioral changes in PDD mice through forced swimming experiments,tail suspension experiments and open field experiments.Nissl staining was used to observe the histological changes of hippocampal neurons in PDD mice.The qRT-PCR and Western blot experiments were used to detect the expression of brain derived neurotrophic factor(BDNF),calcineurin,cAMP responsive element binding protein(CREB)and transcriptional coactivator 1(CRTC1)regulated by CREB in the hippocampal neurons of mice in each group.ELISA detected the levels of 5-hydroxytryptamine(5-HT),dopamine(DA),and norepinephrine(NE)in the hippocampus of mice in each group.Results PDD model mice increased the immobility time of forced swimming test(FST)and tail suspension test(TST),damaged hippocampal neurons,inhibited the expressions of BDNF,calcineurin,CREB and CRTC1,enhanced the expressions of salt induced kinase 2(SIK2)and p-TRTC1 and reduced the levels of 5-HT,DA and NE.ZSD can reverse the impact of PDD modeling,especially in the ZSD medium and high concentration groups.Conclusion ZSD can increase the expressions of monoamine neurotransmitters 5-HT,DA and NE through the CRTC1/CREB/BDNF signaling path-way,thereby repairing the hippocampal neuronal damage in PDD mice and exerting antidepressant effects.It provides a scientific basis for the application of ZSD in the clinical treatment of PDD and new ideas for the treatment of PDD with traditional Chinese medicine.
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