【目的】探讨邓铁涛教授健脑1方对血管性痴呆(VD)大鼠学习记忆能力的影响,并从分子生物学角度探讨其作用机制。【方法】采用双侧颈总动脉永久性结扎法复制VD动物模型,将60只SD雄性大鼠随机分为假手术组、VD模型组、中药高剂量组(剂量为5...【目的】探讨邓铁涛教授健脑1方对血管性痴呆(VD)大鼠学习记忆能力的影响,并从分子生物学角度探讨其作用机制。【方法】采用双侧颈总动脉永久性结扎法复制VD动物模型,将60只SD雄性大鼠随机分为假手术组、VD模型组、中药高剂量组(剂量为57.6 g·kg-1·d-1)、中药低剂量组(剂量为14.4 g·kg-1·d-1)及尼莫地平组(剂量为5.4 mg·kg-1·d-1),给药30 d后采用Morris水迷宫检测各组大鼠的学习记忆能力,观察大鼠海马组织学改变,采用荧光定量法检测大鼠海马NR2B m RNA表达水平。【结果】水迷宫定位航行试验检测结果提示:第3天,与假手术组比较,模型组大鼠逃避潜伏期显著延长(P<0.05);第4天,中药高剂量组大鼠逃避潜伏期较模型组显著下降(P<0.05)。空间探索试验结果显示:60 s内中药高剂量组大鼠穿越平台的次数显著高于模型组,差异有统计学意义(P<0.01),各组停留在平台所在象限的时间与模型组比较差异均无统计学意义(P>0.05)。各组海马组织病理检查可见模型组大鼠海马CA1区神经细胞丢失,神经细胞核碎裂、核膜不清、核仁消失,神经细胞收缩,胞浆嗜酸性增强,胶质细胞反应性增生;中药高、低剂量组海马CA1区可见神经元细胞损伤,病变损伤程度均较模型组显著减轻。尼莫地平组、中药高剂量组NR2B m RNA的表达较模型组显著升高,差异均有统计学意义(P<0.05);中药低剂量组有增高NR2B m RNA表达的趋势,但差异无统计学意义(P>0.05)。【结论】健脑1方可显著改善血管性痴呆大鼠学习记忆能力,其作用可能与减少海马组织神经元损伤程度,上调海马NR2B m RNA表达有关。展开更多
Hyperexcitability of neural network is a key neurophysiological mechanism in several neurological disorders including epilepsy, neuropathic pain, and tinnitus. Although standard paradigm of pharmacological management ...Hyperexcitability of neural network is a key neurophysiological mechanism in several neurological disorders including epilepsy, neuropathic pain, and tinnitus. Although standard paradigm of pharmacological management of them is to suppress this hyperexcitability, such as having been exemplified by the use of certain antiepileptic drugs, their frequent refractoriness to drug treatment suggests likely different pathophysiological mechanism. Because the pathogenesis in these disorders exhibits a transition from an initial activity loss after injury or sensory deprivation to subsequent hyperexcitability and paroxysmal discharges, this process can be regarded as a process of functional compensation similar to homeostatic plasticity regulation, in which a set level of activity in neural network is maintained after injury-induced activity loss through enhanced network excitability. Enhancing brain activity, such as cortical stimulation that is found to be effective in relieving symptoms of these disorders, may reduce such hyperexcitability through homeostatic plasticity mechanism. Here we review current evidence of homeostatic plasticity in the mechanism of acquired epilepsy, neuropathic pain, and tinnitus and the effects and mechanism of cortical stimulation. Establishing a role of homeostatic plasticity in these disorders may provide a theoretical basis on their pathogenesis as well as guide the development and application of therapeutic approaches through electrically or pharmacologically stimulating brain activity for treating these disorders.展开更多
ObjectiveThe aim of the study is to explore the molecular mechanism of Yadanzi(Brucea javanica)in the treatment of glioblastoma(GBM)by using the methods of bioinformatics and network pharmacology.Methods The Tradition...ObjectiveThe aim of the study is to explore the molecular mechanism of Yadanzi(Brucea javanica)in the treatment of glioblastoma(GBM)by using the methods of bioinformatics and network pharmacology.Methods The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and literature retrieval method were applied to obtain the active ingredients of Yadanzi(Brucea javanica),and to predict the relevant targets of the active ingredients.The GBM-related targets were retrieved and screened through the Gene Expression Profling Interactive Analysis(GEPIA)database,and mapped to each other with the targets of the components of Yadanzi(Brucea javanica)to obtain the intersection targets.The GBM differentially expressed gene targets were imported into the String database to obtain the protein interaction relationship,the Cytoscape software was used to draw the protein interaction network,the Cytobba and MCODE plug-ins were used to screen the core genes and important protein interaction modules,and the GEPIA database was applied to make survival analysis of the core genes.The network map of“active ingredients-targets”was constructed through the Cytoscape 3.6.1 software.Gene Ontology(GO)biological function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis for GBM differentially expressed genes were performed through the DAVID database.ResultsThrough TCMSP and literature retrieval,23 potential active ingredients and 129 related targets were obtained from Yadanzi(Brucea javanica).In the GEPIA database,247 GBM differentially expressed genes were screened,including 113 upregulated genes and 134 downregulated genes.After mapping with the targets related to the active ingredients of Yadanzi(Brucea javanica),six intersection targets were obtained,that is,the potential action targets of Yadanzi(Brucea javanica)in treating GBM,including MMP2,HMOX1,BIRC5,EGFR,CCNB2,and TOP2A.Cytoscape software was applied to build an“active ingredient-action target”network.Two active ingredients and five action targets of β-sitosterol(BS)and luteolin were found,and the targets were mainly concentrated in BS.It was found by KEGG pathway enrichment analysis that GBM differentially expressed genes were mainly involved in signaling pathways related to Staphylococcus aureus infection,phagosome formation,tuberculosis and systemic lupus erythematosus and other infectious and autoimmune diseases.It was found by GO enrichment analysis that the GBM differentially expressed genes mainly involved such biological processes(BP)as the processing and presentation of exogenous antigenic peptides and polysaccharide antigens through MHC Il molecules,y-interferon-mediated signaling pathways,extracellular matrix composition,and chemical synapses transmission;it involved cellular components such as cell junctions,axon terminal buttons,extracellular space,vesicle membranes for endocytosis,and MHC Il protein complexes;molecular functions such as calcium-mediated ionic protein binding,MHC Il molecular receptor activity,immunoglobulin binding,and phospholipase inhibitor activity were also involved.Survival analysis was conducted by GEPIA on the top 37 core targets in degree value,and a total of five genes related to GBM prognosis were obtained.Among them,FN1 and MMP2 were highly expressed while GABRD(v-aminobutyric acid A receptor delta subunit),RBFOX1,and SLC6A7 were expressed at a low level in cancer patients.Conclusion The pathogenesis of GBM is closely related to the human immune system,and BS and luteolin may be the main material basis of Yadanzi(Brucea javanica)for the treatment of GBM and the improvement of prognosis.The molecular mechanism may be related to the physical barrier formed by destroying the tumor cell stromal 68 Treatment of Glioblastoma Based on Bioinformatics and Network Pharmacology Zhao,Si.molecules and its involvement in tumor immune response.展开更多
Stroke is a major cause of severe disability and death.Xiao-Xu-Ming decoction(XXMD)is an effective prescription for stroke and its sequelae,while its effective ingredients and mechanism are still unclear.In the presen...Stroke is a major cause of severe disability and death.Xiao-Xu-Ming decoction(XXMD)is an effective prescription for stroke and its sequelae,while its effective ingredients and mechanism are still unclear.In the present study,we aimed to explore the effective ingredients and mechanism of XXMD in treating cerebral ischemia using network pharmacology.The main chemical components and targets of 12 herbs of XXMD were obtained by the TCMSP database and analysis platform database.The active components in XXMD were screened according to oral utilization and drug-like properties.Then,the cerebral ischemia targets were obtained through GeneCards,OMIM,TTD,Diligent and Drugbank databases.We analyzed the pathophysiological processes and pathways involved in the treatment of cerebral ischemia with XXMD by using the Metascape data analysis platform.Results showed thatβ-sitosterol,kaempferol,quercetin,stigmasterol,wogonin,and catechins might be the potential core active ingredients of XXMD in the treatment of cerebral ischemia.The therapeutic effect of XXMD on stroke was mainly exerted through regulating neuroinflammatory response and neurovascular protection.Furthermore,the anti-neuroinflammation and neurovascular protection of XXMD were further confirmed using cerebral ischemia rats.Collectively,our findings revealed that the mechanism of XXMD on the treatment of cerebral ischemia was related to anti-neuroinflammation and neurovascular protection.展开更多
文摘【目的】探讨邓铁涛教授健脑1方对血管性痴呆(VD)大鼠学习记忆能力的影响,并从分子生物学角度探讨其作用机制。【方法】采用双侧颈总动脉永久性结扎法复制VD动物模型,将60只SD雄性大鼠随机分为假手术组、VD模型组、中药高剂量组(剂量为57.6 g·kg-1·d-1)、中药低剂量组(剂量为14.4 g·kg-1·d-1)及尼莫地平组(剂量为5.4 mg·kg-1·d-1),给药30 d后采用Morris水迷宫检测各组大鼠的学习记忆能力,观察大鼠海马组织学改变,采用荧光定量法检测大鼠海马NR2B m RNA表达水平。【结果】水迷宫定位航行试验检测结果提示:第3天,与假手术组比较,模型组大鼠逃避潜伏期显著延长(P<0.05);第4天,中药高剂量组大鼠逃避潜伏期较模型组显著下降(P<0.05)。空间探索试验结果显示:60 s内中药高剂量组大鼠穿越平台的次数显著高于模型组,差异有统计学意义(P<0.01),各组停留在平台所在象限的时间与模型组比较差异均无统计学意义(P>0.05)。各组海马组织病理检查可见模型组大鼠海马CA1区神经细胞丢失,神经细胞核碎裂、核膜不清、核仁消失,神经细胞收缩,胞浆嗜酸性增强,胶质细胞反应性增生;中药高、低剂量组海马CA1区可见神经元细胞损伤,病变损伤程度均较模型组显著减轻。尼莫地平组、中药高剂量组NR2B m RNA的表达较模型组显著升高,差异均有统计学意义(P<0.05);中药低剂量组有增高NR2B m RNA表达的趋势,但差异无统计学意义(P>0.05)。【结论】健脑1方可显著改善血管性痴呆大鼠学习记忆能力,其作用可能与减少海马组织神经元损伤程度,上调海马NR2B m RNA表达有关。
基金supported in part by the NIH DA039530(to XJ)a grant from the CURE Epilepsy Foundation(to XJ)
文摘Hyperexcitability of neural network is a key neurophysiological mechanism in several neurological disorders including epilepsy, neuropathic pain, and tinnitus. Although standard paradigm of pharmacological management of them is to suppress this hyperexcitability, such as having been exemplified by the use of certain antiepileptic drugs, their frequent refractoriness to drug treatment suggests likely different pathophysiological mechanism. Because the pathogenesis in these disorders exhibits a transition from an initial activity loss after injury or sensory deprivation to subsequent hyperexcitability and paroxysmal discharges, this process can be regarded as a process of functional compensation similar to homeostatic plasticity regulation, in which a set level of activity in neural network is maintained after injury-induced activity loss through enhanced network excitability. Enhancing brain activity, such as cortical stimulation that is found to be effective in relieving symptoms of these disorders, may reduce such hyperexcitability through homeostatic plasticity mechanism. Here we review current evidence of homeostatic plasticity in the mechanism of acquired epilepsy, neuropathic pain, and tinnitus and the effects and mechanism of cortical stimulation. Establishing a role of homeostatic plasticity in these disorders may provide a theoretical basis on their pathogenesis as well as guide the development and application of therapeutic approaches through electrically or pharmacologically stimulating brain activity for treating these disorders.
文摘ObjectiveThe aim of the study is to explore the molecular mechanism of Yadanzi(Brucea javanica)in the treatment of glioblastoma(GBM)by using the methods of bioinformatics and network pharmacology.Methods The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and literature retrieval method were applied to obtain the active ingredients of Yadanzi(Brucea javanica),and to predict the relevant targets of the active ingredients.The GBM-related targets were retrieved and screened through the Gene Expression Profling Interactive Analysis(GEPIA)database,and mapped to each other with the targets of the components of Yadanzi(Brucea javanica)to obtain the intersection targets.The GBM differentially expressed gene targets were imported into the String database to obtain the protein interaction relationship,the Cytoscape software was used to draw the protein interaction network,the Cytobba and MCODE plug-ins were used to screen the core genes and important protein interaction modules,and the GEPIA database was applied to make survival analysis of the core genes.The network map of“active ingredients-targets”was constructed through the Cytoscape 3.6.1 software.Gene Ontology(GO)biological function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis for GBM differentially expressed genes were performed through the DAVID database.ResultsThrough TCMSP and literature retrieval,23 potential active ingredients and 129 related targets were obtained from Yadanzi(Brucea javanica).In the GEPIA database,247 GBM differentially expressed genes were screened,including 113 upregulated genes and 134 downregulated genes.After mapping with the targets related to the active ingredients of Yadanzi(Brucea javanica),six intersection targets were obtained,that is,the potential action targets of Yadanzi(Brucea javanica)in treating GBM,including MMP2,HMOX1,BIRC5,EGFR,CCNB2,and TOP2A.Cytoscape software was applied to build an“active ingredient-action target”network.Two active ingredients and five action targets of β-sitosterol(BS)and luteolin were found,and the targets were mainly concentrated in BS.It was found by KEGG pathway enrichment analysis that GBM differentially expressed genes were mainly involved in signaling pathways related to Staphylococcus aureus infection,phagosome formation,tuberculosis and systemic lupus erythematosus and other infectious and autoimmune diseases.It was found by GO enrichment analysis that the GBM differentially expressed genes mainly involved such biological processes(BP)as the processing and presentation of exogenous antigenic peptides and polysaccharide antigens through MHC Il molecules,y-interferon-mediated signaling pathways,extracellular matrix composition,and chemical synapses transmission;it involved cellular components such as cell junctions,axon terminal buttons,extracellular space,vesicle membranes for endocytosis,and MHC Il protein complexes;molecular functions such as calcium-mediated ionic protein binding,MHC Il molecular receptor activity,immunoglobulin binding,and phospholipase inhibitor activity were also involved.Survival analysis was conducted by GEPIA on the top 37 core targets in degree value,and a total of five genes related to GBM prognosis were obtained.Among them,FN1 and MMP2 were highly expressed while GABRD(v-aminobutyric acid A receptor delta subunit),RBFOX1,and SLC6A7 were expressed at a low level in cancer patients.Conclusion The pathogenesis of GBM is closely related to the human immune system,and BS and luteolin may be the main material basis of Yadanzi(Brucea javanica)for the treatment of GBM and the improvement of prognosis.The molecular mechanism may be related to the physical barrier formed by destroying the tumor cell stromal 68 Treatment of Glioblastoma Based on Bioinformatics and Network Pharmacology Zhao,Si.molecules and its involvement in tumor immune response.
基金National Natural Science Foundation of China(Gr ant No.81473383)the Medical and Health Innovation Project o Chinese Academy of Medical Sciences(Grant No.2016-I2M-3-007)Innovation Fund for Graduate of Beijing Union Medical College(Grant No.2018-1007-04)。
文摘Stroke is a major cause of severe disability and death.Xiao-Xu-Ming decoction(XXMD)is an effective prescription for stroke and its sequelae,while its effective ingredients and mechanism are still unclear.In the present study,we aimed to explore the effective ingredients and mechanism of XXMD in treating cerebral ischemia using network pharmacology.The main chemical components and targets of 12 herbs of XXMD were obtained by the TCMSP database and analysis platform database.The active components in XXMD were screened according to oral utilization and drug-like properties.Then,the cerebral ischemia targets were obtained through GeneCards,OMIM,TTD,Diligent and Drugbank databases.We analyzed the pathophysiological processes and pathways involved in the treatment of cerebral ischemia with XXMD by using the Metascape data analysis platform.Results showed thatβ-sitosterol,kaempferol,quercetin,stigmasterol,wogonin,and catechins might be the potential core active ingredients of XXMD in the treatment of cerebral ischemia.The therapeutic effect of XXMD on stroke was mainly exerted through regulating neuroinflammatory response and neurovascular protection.Furthermore,the anti-neuroinflammation and neurovascular protection of XXMD were further confirmed using cerebral ischemia rats.Collectively,our findings revealed that the mechanism of XXMD on the treatment of cerebral ischemia was related to anti-neuroinflammation and neurovascular protection.
