基于网络药理学探讨宁动颗粒治疗抽动-秽语综合征的作用机制  

Exploration on the action mechanism of Ningdong granules in the treatment of Tourette syndrome based on network pharmacology

作　　者：郑晓燕 赵林 ZHENG Xiaoyan;ZHAO Lin

机构地区：[1]山东中医药大学,山东济南250014 [2]山东第一医科大学附属省立医院,山东济南250021

出　　处：《中医临床研究》2024年第30期136-143,共8页Clinical Journal Of Chinese Medicine

基　　金：国家中医药管理局第五批全国中医临床优秀人才研修项目(国中医药人教函[2022]1号)。

摘　　要：目的:通过网络药理学和分子对接技术探讨宁动颗粒治疗抽动-秽语综合征(Tourette Syndrome,TS)的作用机制。方法:运用中药系统药理学数据库与分析平台(TCMSP)、BETMAN-TCM数据库检索宁动颗粒各中药的活性成分及其作用靶点,通过OMIM、DrugBank、GeenCards数据库检索TS相关疾病靶点,将两者取交集,获得宁动颗粒治疗TS的关键靶点,将关键靶点导入STRING数据库,获取蛋白质相互作用信息,利用Cytoscape 3.7.2软件构建蛋白质-蛋白质相互作用(PPI)网络并进行可视化分析,获得核心靶点。运用Metascape数据库对核心靶点进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)通路富集分析。运用AutoDock Vina软件对宁动颗粒治疗TS的有效核心靶点与宁动颗粒中中药对应的活性成分进行分子对接,并进行可视化展示。结果:获取宁动颗粒活性成分180个,共对应643个靶点基因、TS相关靶点1 085个,关键靶点有128个,对关键靶点进行PPI网络构建并进行拓扑分析,根据度值大于平均值共筛选出39个核心靶点。KEGG通路分析主要涉及神经活性配体-受体相互作用、多巴胺能突触、5-羟色胺能突触、钙信号通路、环磷酸腺苷(Cyclic Adenosine Monophosphate,cAMP)信号通路、白细胞介素(Interleukin,IL)-17信号通路等。溶质载体家族6成员3(Solute Carrier Family 6 Member 3,SLC6A3)与豆甾醇亲和力最高,其次是SLC6A3和槲皮素、溶质载体家族6成员4(Solute Carrier Family 6 Member 4,SLC6A4)和球豆碱、FOS原癌基因(Fos Proto-Oncogene,FOS)和槲皮素等。这些可能是宁动颗粒治疗TS的重要活性成分。结论:宁动颗粒可通过“多成分-多靶点-多通路”发挥神经保护、抗炎、免疫应答等作用,从而治疗TS。Objective: To study the mechanism of Ningdong granules( 宁动颗粒) in the treatment of Tourette syndrome(TS) by network pharmacology and molecular docking techniques. Methods: TCMSP and BETMAN-TCM database were used to retrieve the active constituents and target sites of Ningdong granules. OMIM, Drug Bank and Geen Cards database were used to retrieve the key targets of TS related diseases, and the key targets of Ningdong granules in treating TS were obtained by intersection of the two. Key targets were imported into STRING database to obtain protein interaction information, PPI network was constructed by Cytoscape 3.7.2 software, and the core targets were obtained by visual analysis. The GO and KEGG analyses of the core targets were carried out using the Metascape database. Auto Dock Vina software was used to perform molecular docking between the core target of Ningdong granules for TS treatment and the corresponding active components of traditional Chinese medicine in Ningdong granules, and visualization was performed. Results: A total of 180 active components of Ningdong granules were obtained, corresponding to a total of 643 target genes, 1 085 TS-related targets and 128 key targets. PPI network was constructed for key targets, and topological analysis was carried out. A total of 39 core targets were screened out according to the degree value, which was higher than the average value. KEGG pathway analysis mainly involved neuroactive ligand-receptor interaction, dopaminergic synapse, 5-hydroxytryptaminergic synapse, calcium signaling pathway, c AMP signaling pathway, IL-17 signaling pathway, etc. SLC6A3 had the highest affinity with stigasterol, followed by SLC6A3 and quercetin, SLC6A4 and sphaerine, and FOS and quercetin. They may be important active ingredients of Ningdong granules in the treatment of TS. Conclusion: Ningdong granules can play the role of neuroprotection, anti-inflammation and immune response through the mechanism of Multi-components-Multi-targets-Multi-pathways, and plays a therapeutic ro

关 键 词：宁动颗粒 抽动-秽语综合征 网络药理学 分子对接 作用机制 

分 类 号：R272[医药卫生—中医儿科学]