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
为探讨帕金森病(PD)模型大鼠外侧缰核(LHb)中谷氨酸能神经元的电活动变化及其对5-羟色胺2C(5-HT_(2C))受体刺激的反应,阐明LHb和5-HT_(2C)受体在PD神经生物学机制中发挥的作用,通过6-羟多巴胺(6-OHDA)损毁单侧黑质致密部(substantia nig...为探讨帕金森病(PD)模型大鼠外侧缰核(LHb)中谷氨酸能神经元的电活动变化及其对5-羟色胺2C(5-HT_(2C))受体刺激的反应,阐明LHb和5-HT_(2C)受体在PD神经生物学机制中发挥的作用,通过6-羟多巴胺(6-OHDA)损毁单侧黑质致密部(substantia nigra pars compacta,SNc)建立PD模型,采用细胞外记录的方法,观察假手术组与单侧SNc损毁组大鼠LHb中谷氨酸能神经元的电活动。结果显示:与假手术组大鼠相比,损毁组大鼠LHb中谷氨酸能神经元的电活动增强,表现为爆发式放电活动增强(P<0.05);LHb中局部注射5-HT_(2C)受体激动剂Ro60-0175后,两组大鼠的神经元放电频率虽均升高(P<0.05),但损毁组大鼠LHb中谷氨酸能神经元放电频率升高持续时间显著长于假手术组,且给药前后神经元的放电形式更趋向于爆发式活动(P<0.05),变异系数明显升高(P<0.05)。结果提示单侧SNc损毁使LHb中谷氨酸能神经元爆发式电活动增强,可能与PD相关抑郁行为发生有关,5-HT_(2C)受体参与了对LHb中谷氨酸能神经元电活动的调节。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.
文摘为探讨帕金森病(PD)模型大鼠外侧缰核(LHb)中谷氨酸能神经元的电活动变化及其对5-羟色胺2C(5-HT_(2C))受体刺激的反应,阐明LHb和5-HT_(2C)受体在PD神经生物学机制中发挥的作用,通过6-羟多巴胺(6-OHDA)损毁单侧黑质致密部(substantia nigra pars compacta,SNc)建立PD模型,采用细胞外记录的方法,观察假手术组与单侧SNc损毁组大鼠LHb中谷氨酸能神经元的电活动。结果显示:与假手术组大鼠相比,损毁组大鼠LHb中谷氨酸能神经元的电活动增强,表现为爆发式放电活动增强(P<0.05);LHb中局部注射5-HT_(2C)受体激动剂Ro60-0175后,两组大鼠的神经元放电频率虽均升高(P<0.05),但损毁组大鼠LHb中谷氨酸能神经元放电频率升高持续时间显著长于假手术组,且给药前后神经元的放电形式更趋向于爆发式活动(P<0.05),变异系数明显升高(P<0.05)。结果提示单侧SNc损毁使LHb中谷氨酸能神经元爆发式电活动增强,可能与PD相关抑郁行为发生有关,5-HT_(2C)受体参与了对LHb中谷氨酸能神经元电活动的调节。
