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基于网络药理学分析“钩藤-白芍”治疗小儿抽动障碍的作用机制
吴 吉,朱沁泉,张 涤
0
(湖南中医药大学第一附属医院,湖南 长沙,410007)
摘要:
目的:运用网络药理学方法探讨钩藤、白芍治疗小儿抽动障碍(TD)的作用靶点及相关信号通路,以明确其作用机制。方法:在TCMSP数据库中检索钩藤、白芍化学成分并筛选作用靶点,并检索相关文献进行补充;从GENECARD、OMIM、TTD及DrugBank数据库检索与抽动障碍相关的疾病靶点,利用Cytoscape 3.7.0软件构建化合物-靶点网络,并筛选核心网络,进行GO功能和KEGG通路富集分析。结果:共筛选出钩藤治疗TD的化合物30种,与之相对应的作用靶点590个;白芍治疗TD的化合物7种,与之相对应的作用靶点81个。活性成分靶点与抽动障碍疾病靶点的交集基因共37个,交集基因的PPI网络共包含节点37个、边198条,平均节点度值为9.89。GO分析结果显示,上述交集基因的分子功能主要包括G蛋白耦联受体活性、儿茶酚胺结合、神经递质受体活性等,生物过程主要涉及腺苷酸环化酶激活肾上腺素能受体信号、化学突触传递等,细胞组分主要包括突触膜固有成分、突触后膜等。KEGG分析结果显示,信号通路主要涉及神经活性配体-受体相互作用信号通路、钙信号通路、cGMP-PKG信号通路、cAMP信号通路、PI3K-Akt信号通路等。结论:本研究初步验证了钩藤-白芍治疗TD的药理学作用机制,为进一步从细胞生物学层面验证其作用机制奠定了基础。
关键词:  小儿  抽动障碍  钩藤-白芍  网络药理学  作用机制
DOI:
Mechanism of action of uncaria-Radix Paeoniae Alba in treatment of tic disorder in children based on network pharmacology
WU Ji,ZHU Qinquan,ZHANG Di
(The First Affiliated Hospital of Hunan University of Chinese Medicine,Changsha 410007,Hunan,China)
Abstract:
Objective:To investigate the mechanism of action of uncaria and Radix Paeoniae Alba in the treatment of tic disorder (TD) in children by analyzing their action targets and related signaling pathways based on network pharmacology.Methods:TCMSP database was used to screen out the chemical components and action targets of uncaria and Radix Paeoniae Alba,and a literature review was performed for supplementation.GENECARD,OMIM,TTD,and DrugBank databases were used to screen out the disease targets associated with TD,and Cytoscape 3.7.0 software was used to construct a component-target network and screen out the core network.Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed.Results:A total of 30 components of uncaria and 590 corresponding action targets were screened out,and a total of 7 components of Radix Paeoniae Alba and 81 corresponding action targets were screened out.There were 37 intersecting genes between the targets of active components and the disease targets of TD,and the PPI network of the intersecting genes had 37 nodes and 198 lines,with a mean node degree of 9.89.GO analysis showed that the molecular functions of the above intersecting genes mainly included activity of G protein-coupled receptor,binding of catecholamine,and activity of neurotransmitter receptor.Biological processes mainly involved activation of adrenergic receptor signal by adenylate cyclase and chemical synapse transmission,and cellular components mainly included intrinsic components of the synaptic membrane and postsynaptic membrane.KEGG analysis showed that the signaling pathways mainly involved neuroactive ligand-receptor interaction signaling pathway,calcium signaling pathway,cGMP-PKG signaling pathway,cAMP signaling pathway,and PI3K-Akt signaling pathway.Conclusion:This study preliminarily validates the pharmacological mechanism of action of uncaria-Radix Paeoniae Alba in the treatment of TD,which lays a foundation for further validation of their mechanism of action at the level of cell biology.
Key words:  child  tic disorder  uncaria-Radix Paeoniae Alba  network pharmacology  mechanism of action

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