The Effects Of Jieyu Anshen Granule On A Mouse Model Of Post-stroke Depression And Its Mechanisms

Objective:This research is aimed to observe the therapeutic effect of Jieyu Anshen granules(JY)on post-stroke depression(PSD)mouse model and its mechanisms,which provides experimental evidence for the clinical application of JY.Methods:PSD mice model was established by bilateral common carotid artery occlusion(BCCO)followed by chronic unpredictable mild stress(CUMS).The mice were divided into six matched groups:control or sham operated(CON),BCCO followed by CUMS(MODEL),BCCO+CUMS+10 mg/kg escitalopram(ESCIT),BCCO+CUMS+O.75 g/kg JY(JY0.75),BCCO+CUMS+1.5 g/kg JY(JY1.5)and BCCO+CUMS+3 g/kg JY(JY3)groups.BCCO after 96 h,except CON group,the experimental groups received a 28-day CUMS,and daily administration of JY and escitalopram at appropriate doses for 28 days.The sucrose preference test,forced swim test and tail suspension test were used to assess depression-like behaviors of mice.The mice were sacrificed at the end of administration.The serum was separated.The hippocampus was removed from the brain.Concentrations of norepinephrine(NE),dopamine(DA)and 5-hydroxytryptamine(5-HT)in the hippocampus were determined by high performance liquid chromatography.The expression of 5-hydroxytryptamine 1A receptor(5-HT1AR),brain derived neurotrophic factor(BDNF)and glucocorticoid recepyor(GR)in hippocampus of mcie were evaluated by western blot.The serum corticosterone(CORT)level,and the levels of TNF-? and IL-18 in serum and hippocampus of mice were evaluated by ELISA.Results:1.Compared with the CON group,the MODEL group had reduced sucrose preference on day 28(P<0.05).Compared with the MODEL group,the ESCIT and JY1.5 groups showed a significant increased preference for the sucrose solution on day 28(P<0.05),suggesting its effects on the anhedonia of PSD mice.2.Compared with the CON group,the swimming immobility time was significantly increased(P<0.05).Compared with the MODEL group,the immobility time of PSD mice in the JY0.75 and 1.5 groups was significantly reduced(P<0.05),suggesting its effects on the despair of PSD mice.3.Compared with the CON group,the suspension immobility time was significantly increased(P<0.05).Compared with the MODEL group,the immobility time of PSD mice in the JY 1.5 and JY3 groups was significantly reduced(P<0.05,P<0.01),suggesting its effects on the despair of PSD mice.4.Compared with the CON group,the levels of DA,NE and 5-HT in hippocampus were significantly decreased in the MODEL group(P<0.05,P<0.01).Compared with the MODEL group,the levels of 5-HT in ESCIT group,the levels of 5-HT,NE and DA in hippocampus in JY1.5,and the level of NE in JY3 groups were significantly increased(P<0.05,P<0.01).5.Compared with the CON group,the expression of 5-HT1AR was significantly decreased in hippocampus in the MODEL group(P<0.01).Compared with the MODEL group,the expression of 5-HT1AR in hippocampus were significantly increased in JY1.5 and JY3 groups(P<0.01).Compared with the CON group,the expression of BDNF was significantly decreased in hippocampus in the MODEL group(P<0.01).Compared with the MODEL group,the expression of BDNF in hippocampus were significantly increased in JY 1.5 and JY3 groups(P<0.01),suggesting its effects on the expression of 5-HT1AR and BDNF in hippocampus of PSD mice.6.The level of serum CORT in the MODEL group was significantly increased than that in the CON group(P<0.01).Compared with the MODEL group,the level of serum CORT was significantly decreased in ESCIT and JY3 groups(P<0.05,P<0.01).Compared with the CON group,the expression of GR in hippocampus was significantly decreased in the MODEL group(P<0.01).Compared with the MODEL group,the expression of GR in hippocampus was significantly increased in JY1.5 and JY3 groups(P<0.01),suggesting its effects on the inbibition of HPA axis of PSD mice.7.Compared with the CON group,the TNF-? level in serum and hippocampus was significantly increased(P<0.05,P<0.01).Compared with the MODEL group,the TNF-? level in serum in JY3 group,the TNF-? level in hippocampus in ESCIT,JY0.75,1.5 and 3 groups were significantly decreased(P<0.05,P<0.01).Compared with the CON group,the IL-18 level in serum and hippocampus was significantly increased(P<0.05,P<0.01).Compared with the MODEL group,the IL-18 level in serum and hippocampus in ESCIT,JY1.5 and 3 groups were significantly decreased(P<0.05,P<0.01).Conclusions:1.PSD mouse model can be successfully established by BCCO in combination with CUMS.2.JY has exerted antidepressant effect on PSD mouse model,which can significantly improve the anhedonia and despair.5.The mechanisms of antidepressant effect of JY on PSD mice are accompanied with regulating the level of monoamine neurotransmitters and its receptors in hippocampus,up-regulating BDNF expression in hippocampus,inhibiting the hyperthyroidism of HPA axis and inhibiting neuroinflammation.