基于网络药理学探讨牛膝防治动脉粥样硬化的分子机制  

Study on the molecular mechanism of Achyranthis Bidentatae Radix in treatment of atherosclerosis based on network pharmacology

作　　者：王健[1] 王涛 李敬田[2] 张泉[2] 郝杰 曹步凡 王世发 WANG Jian;WANG Tao;LI Jingtian;ZHANG Quan;HAO Jie;CAO Bufan;WANG Shifa(Department of Internal Medicine,Weifang Medical University,Weifang 261053,China;Department of Cardiology,the Affiliated Hospital of Weifang Medical University)

机构地区：[1]潍坊医学院内科学教研室,山东潍坊261053 [2]潍坊医学院附属医院心血管内科

出　　处：《潍坊医学院学报》2021年第2期129-134,共6页Acta Academiae Medicinae Weifang

基　　金：山东省中医药科技发展计划项目资助课题(项目编号:2019-0426)。

摘　　要：目的基于网络药理学的方法,预测牛膝治疗动脉粥样硬化(AS)的有效成分和作用靶点,探讨其可能的分子机制。方法在TCMSP数据库筛选出牛膝的有效成分,并在GeneCards数据库匹配各有效成分的靶点,利用DisGeNET数据库筛选出与AS相关的靶点,基于Cytoscape软件构建有效成分-靶点-AS关系网络图。利用DAVID数据库对关键靶点进行KEGG通路富集分析和GO分析,并绘制网络图。结果筛选出牛膝中有效成分7种,与其相关的作用靶点共311个,选取与AS发生最相关的5种有效成分进一步分析,最终筛选出与AS相关的靶点537个,主要涉及AGT,LDLR,Sirt1等靶点,并筛选出AMPK,cGMP-PKG,RAS,cAMP等多条信号通路,参与牛膝抗AS的作用。结论牛膝可能主要通过黄连素、黄连碱等有效成分,共同调节Sirt1,AGT及LDLR等相关靶点,调控AMPK信号通路、cAMP信号通路、细胞凋亡等发挥调脂、抗炎、改善内皮功能等作用防治动脉粥样硬化。Objective To explore the effective ingredients and targets of Achyranthis Bidentatae Radix for the treatment of atherosclerosis based on network pharmacology,and predict its possible molecular mechanism.Methods The effective ingredients of Achyranthis Bidentatae Radix were screened in the TCMSP database.Matching the targets of each active ingredient in the GeneCards database and using the DisGeNET database to screen out the targets related to atherosclerosis.Building the effective ingredient-target-atherosclerosis relationship network diagram with the Cytoscape software.KEGG pathway enrichment analysis of the key targets was performed by the DAVID database with the target-pathway network diagram and the effective ingredient-pathway network diagram were drawn.Results Through experiments,a total of 7 effective ingredients in Achyranthis Bidentatae Radix and 311 related effective targets were screened out.A total of 537 targets related to atherosclerosis were obtained,mainly including AGT,LDLR,Sirt1 and other related targets.And multiple signaling pathways such as AMPK signaling pathway,cGMP-PKG signaling pathway,RAS signaling pathway,and cAMP signaling pathway also play roles in the treatment of atherosclerosis.Conclusion Achyranthes Bidentata Radix may be used for the treatment of AS by regulating Sirt1 and other targets,regulating AMPK signaling pathway,cAMP signaling pathway,apoptosis and other pathways to regulate lipids,play anti-inflammatory roles and improve endothelium etc.

关 键 词：网络药理学 牛膝 动脉粥样硬化 靶点 信号通路 

分 类 号：R543.5[医药卫生—心血管疾病]