OBJECTIVE To explore the effects and underlying mechanism of Jieyu Anshen granule(JY) in chronic unpredictable mild stress(CUMS)-treated rats after ischemic stroke.METHODS A rat model of post-stroke depression(PSD) wa...OBJECTIVE To explore the effects and underlying mechanism of Jieyu Anshen granule(JY) in chronic unpredictable mild stress(CUMS)-treated rats after ischemic stroke.METHODS A rat model of post-stroke depression(PSD) was developed by additional CUMS procedures after middle cere.bral artery occlusion(MCAO).Sprague-Dawley rats were given 1 g·kg^(-1) and 3 g·kg^(-1) of JY by gastrogavage for 4 weeks.Escitalopram(10 mg·kg^(-1)) served as a reference drug.Behavioral tests including sucrose preference test,forced swim test and open-field test were performed to evaluate the antidepressant effects.Levels of norepinephrine(NE),dopamine(DA) and 5-hydroxytryptamine(5-HT) in rat brain were assayed.The anti-inflammatory activity was evaluated by measuring TNF-α and IL-1β in brain.Serum adrenocorticotropic hormone(ACTH) and corticosterone(CORT) were estimated as indices of hypothalamic-pituitary-adrenal(HPA) axis activity.Western blot analysis was used to evaluate hippo.campal expression of the 5-HT1 A receptor(5-HT_(1A)R) and brain-derived neurotrophic factor(BDNF).RESULTS PSD rats exhibited decreased sucrose consumption and motor activity,increased immobility time(P<0.01).JY treatment reversed the depressive behaviors in PSD rats(P<0.05,P<0.01).Treat.ment with JY resulted in significantly increased levels of NE,DA and 5-HT in the hippocampus and prefrontal cortex(P<0.05,P<0.01),and increased expression of 5-HT_(1A)R and BDNF in the hippocampus(P<0.01).JY treatment significantly down-regulated the levels of TNF-α and IL-1β in hippocampus and prefrontal cortex(P<0.05).Treatment with JY also resulted in significantly decreased ACTH and CORT in serum which had been increased(P<0.05).CONCLUSION These findings suggest that JY treat.ment could ameliorate PSD,and the effects are likely ascribed to inhibiting HPA axis hyperfunction and inflammatory,up-regulating the levels of neurotransmitters(NE,DA and 5-HT),and the expression of hippocampal 5-HT_(1A)R and BDNF.展开更多
基金supported by National Natural Science Foundation of China(8157369)
文摘OBJECTIVE To explore the effects and underlying mechanism of Jieyu Anshen granule(JY) in chronic unpredictable mild stress(CUMS)-treated rats after ischemic stroke.METHODS A rat model of post-stroke depression(PSD) was developed by additional CUMS procedures after middle cere.bral artery occlusion(MCAO).Sprague-Dawley rats were given 1 g·kg^(-1) and 3 g·kg^(-1) of JY by gastrogavage for 4 weeks.Escitalopram(10 mg·kg^(-1)) served as a reference drug.Behavioral tests including sucrose preference test,forced swim test and open-field test were performed to evaluate the antidepressant effects.Levels of norepinephrine(NE),dopamine(DA) and 5-hydroxytryptamine(5-HT) in rat brain were assayed.The anti-inflammatory activity was evaluated by measuring TNF-α and IL-1β in brain.Serum adrenocorticotropic hormone(ACTH) and corticosterone(CORT) were estimated as indices of hypothalamic-pituitary-adrenal(HPA) axis activity.Western blot analysis was used to evaluate hippo.campal expression of the 5-HT1 A receptor(5-HT_(1A)R) and brain-derived neurotrophic factor(BDNF).RESULTS PSD rats exhibited decreased sucrose consumption and motor activity,increased immobility time(P<0.01).JY treatment reversed the depressive behaviors in PSD rats(P<0.05,P<0.01).Treat.ment with JY resulted in significantly increased levels of NE,DA and 5-HT in the hippocampus and prefrontal cortex(P<0.05,P<0.01),and increased expression of 5-HT_(1A)R and BDNF in the hippocampus(P<0.01).JY treatment significantly down-regulated the levels of TNF-α and IL-1β in hippocampus and prefrontal cortex(P<0.05).Treatment with JY also resulted in significantly decreased ACTH and CORT in serum which had been increased(P<0.05).CONCLUSION These findings suggest that JY treat.ment could ameliorate PSD,and the effects are likely ascribed to inhibiting HPA axis hyperfunction and inflammatory,up-regulating the levels of neurotransmitters(NE,DA and 5-HT),and the expression of hippocampal 5-HT_(1A)R and BDNF.
