OBJECTIVE The Ginkgo Leaf Extract and Armillariella Mellea Powders Oral(Yinxingmihuan Koufu Rongye,YXMH),a representative drug for"Treating both Brain and Heart",showed considerable clinical effects in isch⁃...OBJECTIVE The Ginkgo Leaf Extract and Armillariella Mellea Powders Oral(Yinxingmihuan Koufu Rongye,YXMH),a representative drug for"Treating both Brain and Heart",showed considerable clinical effects in isch⁃emic cardiovascular and cerebral vascular diseases.Recently,it is reported that YXMH has the potential for treating myocardial and cerebral ischemia related mental disorders,such as post stroke depression(PSD)and chronic heart disease(CHD)associated anxiety disorder.However,its mechanism has not been clearly elucidated.Meanwhile,increasing evidence revealed that there are close functional links between depression and habenular nucleus.The present study investigates the underlying mechanism of YXMH on attenuating the inflammation of microglia in habenular nucleus through CX3CL1-CX3CR1 axis in in a rat model of PSD.METHODS Rats were randomly devided into sham group,model group,Ginaton group(18 mg·kg^-1),Armillariella Mellea group(600 mg·kg-1),Fluoxetine group(10 mg·kg^-1),YXMH high-dose group(618 mg·kg^-1)and YXMH low-dose group(309 mg·kg^-1).The PSD model was induced by transarterial microembolization combined with sleep deprivation(2-Chloro-D-phenylalanine,PCPA,IH,200 mg·kg^-1,for 3 times,before the behavior test)in SD male rats.Then rats were treated with corresponding medicaments through gavage once a day until 3 weeks later,followed by body mass measurement,neurological deficit score evaluation,gripping strength and thermal withdrawl latency measurement,as well as depression related behavioral indicators,the open field test(OFT)and sucrose preference test.The pathological morphological changes of habenular nucleus was observed by HE staining,the expression of IBA-1 was measured and analyzed by immunohistochemistry staining,and alterations of proteins and genes related to the CX3CL1-CX3CR1 axis were analyzed using Western blotting(CX3CL1,CX3CR1)and real-time polymerase chain reaction(PCR)(CX3CL1,CX3CR1).RESULTS Compared with the sham group,rats in the model group manifested as decreased body mass,deficient neurological behavior and gripping strength,reduced loco⁃motor activity and sugar water consumption,as well as elevated thermal withdrawl latency(P<0.05,P<0.01).Mean⁃while,the pathological morphology of the habenular nucleus on the ischemic hemisphere showed significant neuronal degeneration,microglial proliferation,inflammatory cells and glia cells infiltration,together with up-regualted expression of IBA-1,CX3CL1,CX3CR1 protein and CX3CL1,CX3CR1 mRNA.YXMH attenuated inflammation of microglia in habenular nucleus through improving pathological morphology,inhibiting IBA-1 activation,down-regulating the expres⁃sion of CX3CL1 and CX3CR1 proteins and genes,and thus improved the behavior performance of ischemic injury and depression.CONCLUSION YXMH ameliorates neurological deficit and depressive behavior in rat model of PSD induced by transarterial microembolization combined with sleep deprivation,and the mechanism is probably related to attenu⁃ating inflammation of microglia in habenular nucleus through CX3CL1-CX3CR1 axis.展开更多
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
目的探索单侧基底节卒中后抑郁(post-stroke depression,PSD)患者静息态功能磁共振成像(resting state functional magnetic resonance imaging,rs-fMRI)特征,明确rs-fMRI在单侧基底节PSD患者临床诊治过程中的应用价值。材料与方法纳入4...目的探索单侧基底节卒中后抑郁(post-stroke depression,PSD)患者静息态功能磁共振成像(resting state functional magnetic resonance imaging,rs-fMRI)特征,明确rs-fMRI在单侧基底节PSD患者临床诊治过程中的应用价值。材料与方法纳入45例卒中患者,根据17项汉密尔顿抑郁量表(Hamilton Depression Scale 17,HAMD-17)结果,将被试分为PSD组23例和卒中后非抑郁(nonpost-strokedepression,NPSD)组22例,通过局部一致性(regionalhomogeneity,ReHo)和低频振幅(amplitude of low frequency fluctuations,ALFF)分析方法比较两组被试ReHo、ALFF值存在显著差异的脑区。结果与PSD组相比,NPSD组在左颞极中回、左中央前回(t=5.4428、3.5079,P<0.05)的ReHo值升高,在左梭状回、左楔前叶(t=-3.5528、-4.1124,P<0.05)的ReHo值降低,在右梭状回、右颞下回、左后扣带回、右扣带回、右缘上回、左中央前回、左旁中央小叶、右中央前回(t=3.5149、3.2775、4.6102、3.7343、4.2189、3.8542、4.3429、3.9644,P<0.05)的ALFF值升高,组间差异具有统计学意义(P<0.05,FWE校正)。结论单侧基底节PSD患者默认模式网络、感觉运动网络和社交网络部分脑区出现ReHo和ALFF变化,上述成像特征或为疾病发生发展的关键,明确了rs-fMRI在单侧基底节PSD患者临床诊治过程中的应用价值,这将为探索PSD发生发展机制相关的脑功能研究和疾病预后情况提供参考有助于PSD的早期诊断和干预治疗。展开更多
基金National Natural Science Foundation of China(8187304081403141)
文摘OBJECTIVE The Ginkgo Leaf Extract and Armillariella Mellea Powders Oral(Yinxingmihuan Koufu Rongye,YXMH),a representative drug for"Treating both Brain and Heart",showed considerable clinical effects in isch⁃emic cardiovascular and cerebral vascular diseases.Recently,it is reported that YXMH has the potential for treating myocardial and cerebral ischemia related mental disorders,such as post stroke depression(PSD)and chronic heart disease(CHD)associated anxiety disorder.However,its mechanism has not been clearly elucidated.Meanwhile,increasing evidence revealed that there are close functional links between depression and habenular nucleus.The present study investigates the underlying mechanism of YXMH on attenuating the inflammation of microglia in habenular nucleus through CX3CL1-CX3CR1 axis in in a rat model of PSD.METHODS Rats were randomly devided into sham group,model group,Ginaton group(18 mg·kg^-1),Armillariella Mellea group(600 mg·kg-1),Fluoxetine group(10 mg·kg^-1),YXMH high-dose group(618 mg·kg^-1)and YXMH low-dose group(309 mg·kg^-1).The PSD model was induced by transarterial microembolization combined with sleep deprivation(2-Chloro-D-phenylalanine,PCPA,IH,200 mg·kg^-1,for 3 times,before the behavior test)in SD male rats.Then rats were treated with corresponding medicaments through gavage once a day until 3 weeks later,followed by body mass measurement,neurological deficit score evaluation,gripping strength and thermal withdrawl latency measurement,as well as depression related behavioral indicators,the open field test(OFT)and sucrose preference test.The pathological morphological changes of habenular nucleus was observed by HE staining,the expression of IBA-1 was measured and analyzed by immunohistochemistry staining,and alterations of proteins and genes related to the CX3CL1-CX3CR1 axis were analyzed using Western blotting(CX3CL1,CX3CR1)and real-time polymerase chain reaction(PCR)(CX3CL1,CX3CR1).RESULTS Compared with the sham group,rats in the model group manifested as decreased body mass,deficient neurological behavior and gripping strength,reduced loco⁃motor activity and sugar water consumption,as well as elevated thermal withdrawl latency(P<0.05,P<0.01).Mean⁃while,the pathological morphology of the habenular nucleus on the ischemic hemisphere showed significant neuronal degeneration,microglial proliferation,inflammatory cells and glia cells infiltration,together with up-regualted expression of IBA-1,CX3CL1,CX3CR1 protein and CX3CL1,CX3CR1 mRNA.YXMH attenuated inflammation of microglia in habenular nucleus through improving pathological morphology,inhibiting IBA-1 activation,down-regulating the expres⁃sion of CX3CL1 and CX3CR1 proteins and genes,and thus improved the behavior performance of ischemic injury and depression.CONCLUSION YXMH ameliorates neurological deficit and depressive behavior in rat model of PSD induced by transarterial microembolization combined with sleep deprivation,and the mechanism is probably related to attenu⁃ating inflammation of microglia in habenular nucleus through CX3CL1-CX3CR1 axis.
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.
文摘目的探索单侧基底节卒中后抑郁(post-stroke depression,PSD)患者静息态功能磁共振成像(resting state functional magnetic resonance imaging,rs-fMRI)特征,明确rs-fMRI在单侧基底节PSD患者临床诊治过程中的应用价值。材料与方法纳入45例卒中患者,根据17项汉密尔顿抑郁量表(Hamilton Depression Scale 17,HAMD-17)结果,将被试分为PSD组23例和卒中后非抑郁(nonpost-strokedepression,NPSD)组22例,通过局部一致性(regionalhomogeneity,ReHo)和低频振幅(amplitude of low frequency fluctuations,ALFF)分析方法比较两组被试ReHo、ALFF值存在显著差异的脑区。结果与PSD组相比,NPSD组在左颞极中回、左中央前回(t=5.4428、3.5079,P<0.05)的ReHo值升高,在左梭状回、左楔前叶(t=-3.5528、-4.1124,P<0.05)的ReHo值降低,在右梭状回、右颞下回、左后扣带回、右扣带回、右缘上回、左中央前回、左旁中央小叶、右中央前回(t=3.5149、3.2775、4.6102、3.7343、4.2189、3.8542、4.3429、3.9644,P<0.05)的ALFF值升高,组间差异具有统计学意义(P<0.05,FWE校正)。结论单侧基底节PSD患者默认模式网络、感觉运动网络和社交网络部分脑区出现ReHo和ALFF变化,上述成像特征或为疾病发生发展的关键,明确了rs-fMRI在单侧基底节PSD患者临床诊治过程中的应用价值,这将为探索PSD发生发展机制相关的脑功能研究和疾病预后情况提供参考有助于PSD的早期诊断和干预治疗。
