2018 年第 12 期 第 13 卷

基于网络药理学的川芎抗动脉粥样硬化的机制研究

Study on action mechanism of Chuanxiong in attenuation of atherosclerosis based on network pharmacology

作者：田晋帆吕树铮宋现涛李立志刘玥

英文作者：

单位：100029首都医科大学附属北京安贞医院心内科（田晋帆、吕树铮、宋现涛）；100091北京，中国中医科学院西苑医院心血管中心（李立志、刘玥）

英文单位：

关键词：动脉粥样硬化；网络药理学；川芎

英文关键词：

• 摘要：

• 【摘要】目的    基于网络药理学探讨川芎抗动脉粥样硬化靶标及信号通路。方法    在中药系统药理学数据库和分析平台(TCMSP)中查询川芎组分，筛选类药性≥0.18的化合物，并参照既往文献补充4个常用川芎活性组分用于进一步分析。应用TCMSP数据库查询每种化合物对应的靶标，运用Uniprot数据库查询靶标蛋白对应的基因简称，并剔除非人源靶标，最终得到川芎调控的人源靶标。通过Drugbank数据库、TCMSP数据库、TTD数据库、GAD数据库及既往文献检索动脉粥样硬化人源靶标。将川芎的疾病靶标基因与动脉粥样硬化靶标基因取交集，获得川芎抗人动脉粥样硬化的靶标基因，交集所得的基因通过Cytoscape软件构建成分-靶标网络。将交集得到的基因应用STRING数据库构建蛋白相互作用网络，得到川芎对抗动脉粥样硬化的体内反应网络。在DAVID数据库中进行KEGG通路富集分析，应用Cytoscape软件构建基因-通路网络和成分-通路网络。结果    以类药性≥0.18为限定条件筛选得到20个化合物，并参考既往文献补充4个常用组分，共获得71个川芎调控的疾病靶标和348个人动脉粥样硬化靶标，取交集，获得37个川芎治疗人动脉粥样硬化的靶标。37个基因靶标应用DAVID数据库进行KEGG富集分析，获得与川芎抗动脉粥样硬化相关的通路14个（磷脂酰肌醇3激酶-蛋白激酶B、腺苷酸活化蛋白激酶、肿瘤坏死因子、胰岛素抵抗、血管平滑肌收缩、钙离子、血管内皮生长因子、炎症介质调控的TRP通道、低氧诱导因子1、血小板活化、环磷酸腺苷、Ras、T细胞受体、环磷酸乌苷依赖蛋白激酶G）。结论    川芎通过抑制炎性反应、氧化应激，保护内皮功能，抑制泡沫细胞形成，抑制血管平滑肌细胞增殖迁移，改善血管舒缩功能，抑制血小板聚集，调控细胞死亡等多靶标、多通路改善动脉粥样硬化。

• 【Abstract】Objective    To analyze the targets and pathways by which Chuanxiong attenuates atherosclerosis based on the network pharmacology. Methods    Active compounds of Chuanxiong with drug-likeness≥0.18 from Traditional Chinese Medicine Systems Pharmacology(TCMSP) and compounds with high frequency in available literatures were used for further analysis. Targets of the active compounds were obtained in TCMSP database. Uniprot database was used to retrieve the gene symbols of the targets; the targets of Homo sapiens were obtained. Therapeutic targets of atherosclerosis of Homo sapiens were obtained in Drugbank, TCMSP, TTD, GAD databases and previous literatures. Target genes of Chuanxiong for attenuation of atherosclerosis were obtained by the intersection of the targets of active compounds and the therapeutic targets of atherosclerosis. Compound-target network was established using Cytoscape software. Protein-protein interaction network was constructed by String database. DAVID database was used to enrichment the analysis of target genes. Gene-pathway and compound-pathway were constructed using Cytoscape software. Results    Twenty compounds of Chuanxiong with drug-likeness≥0.18 and 4 common compounds in previous literatures were derived. Seventy-one disease targets of Chuanxiong and 348 targets of atherosclerosis of Homo sapiens were obtained. Thirty-seven gene targets of Chuanxiong for attenuation of atherosclerosis were used for KEGG pathway enrichment analysis in DAVID database; 14 pathways were obtained. Chuanxiong could attenuate atherosclerosis through phosphatidylinositol-3-kinase/protein kinase B, AMP-activated protein kinase, tumor necrosis factor, insulin resistance, vascular smooth muscle contraction， calcium signaling pathway， vascular endothelial growth factor, TRP pathway, hypoxia inducible factor-1, platelet activation, cAMP, Ras pathway, T-cell receptor and cGMP-dependent protein kinase G. Conclusion    Chuanxiong attenuates atherosclerosis by multi-targets and multi-pathways such as inhibiting inflammation and oxidative stress, protecting endothelial function, inhibiting foam cell information and vascular smooth muscle cell proliferation and migration, improving vasoconstriction and vasodilatation, inhibiting platelet aggregation and regulating cell apoptosis.