基于网络药理学探讨加味血脉通2号颗粒抗动脉粥样硬化的分子机制  

Discussion on the molecular mechanism of modified Xuemaitong No.2 Granules( 加味血脉通2 号颗粒)against atherosclerosis based on network pharmacology

作　　者：张卫东[1] 赵权 张琪[2] 廉源沛 朱力 颜晓静[3] ZHANG Weidong;ZHAO Quan;ZHANG Qi;LIAN Yuanpei;ZHU Li;YAN Xiaojing(Pharmacy Department,Changzhou Hospital of Chinese Medicine,Nanjing University of Chinese Medicine,Changzhou,Jiangsu,213003,China;Department of Cardiovascular,Changzhou Hospital of Chinese Medicine,Nanjing University of Chinese Medicine,Changzhou,Jiangsu,213003,China;Changzhou Key Laboratory of Menghe Medical School Human Experience Research and Transformation,Changzhou Hospital of Chinese Medicine,Nanjing University of Chinese Medicine,Changzhou,Jiangsu,213003,China)

机构地区：[1]南京中医药大学附属常州市中医院药学部,江苏常州213003 [2]南京中医药大学附属常州市中医院心血管科,江苏常州213003 [3]南京中医药大学附属常州市中医院,常州市孟河医派人用经验研究与转化重点实验室,江苏常州213003

出　　处：《甘肃中医药大学学报》2024年第2期61-69,共9页Journal of Gansu University of Chinese Medicine

基　　金：常州市科技计划项目(CJ20190068);江苏省科协青年科技人才托举工程(098);常州市青年科技人才托举工程(常科协〔2020〕86);常州市卫生健康青苗人才培养工程(CZQM2020087)。

摘　　要：目的基于网络药理学方法分析加味血脉通2号颗粒抗动脉粥样硬化(AS)的作用靶点及信号通路,进而探讨其潜在作用机制。方法通过中药系统药理学数据库和分析平台(TCMSP),中医药研究整合数据库(TCMID)及Swiss Target Prediction数据库筛选加味血脉通2号颗粒相关活性成分及靶点;通过Gene-Cards、在线人类孟德尔遗传(OMIM)数据库查找与AS相关的靶点,并将二者靶点通过基因标准化后进行映射;运用Cytoscape 3.7.1软件构建“化合物-靶点”网络图,利用STRING数据库绘制蛋白质-蛋白质相互作用(PPI)网络,利用功能注释生物信息学分析平台(DAVID)数据库进行基因本体(GO)功能、京都基因与基因组百科全书(KEGG)通路富集分析。结果共筛选得到活性成分140个,成分相关靶点943个,AS疾病靶点2157个,药物-疾病的交集靶点389个;GO功能富集分析得到GO条目1291个,其中生物过程(BP)条目943个、细胞组成(CC)条目98个、分子功能(MF)条目250个,主要涉及炎症反应、细胞外基质分解、酶结合、类固醇激素受体活性等;KEGG通路富集分析得到信号通路149条,主要涉及Toll样受体信号通路、癌症、肿瘤坏死因子、缺氧诱导因子-1信号通路、磷脂酰肌醇3激酶/蛋白激酶B(PI3K/Akt)信号通路等。结论加味血脉通2号颗粒可能是熊果酸、谷甾醇等通过丝裂原活化蛋白激酶(MAPK)1、MAPK3、MAPK8、白细胞介素(IL)-6、肿瘤坏死因子(TNF)、基质金属蛋白酶(MMP)2、MMP9等多靶点调节炎症反应、细胞凋亡、氧化应激而治疗AS。Objective To analyze the targets and signal pathways of modified Xuemaitong No.2 Granules(加味血脉通2号颗粒)against atherosclerosis(AS)based on network pharmacology,and to explore its potential molecular mechanism.Methods The active components and targets of modified Xuemaitong No.2 Granules were screened by TCMSP,TCMID and Swiss Target Prediction servers;GeneCards and online human Mendelian inheritance(OMIM)databases were used to find AS-related targets,and the two targets were mapped after gene standardization;The“compound-target”network was constructed by Cytoscape 3.7.1 software,and the protein-protein interaction(PPI)network was drawn by STRING database.The gene ontology(GO)function and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed by DAVID database.Results A total of 140 active components,943 component-related targets,2157 AS disease targets,and 389 drug-disease common targets were screened;GO function enrichment analysis obtained 1291 GO entries,including 943 biological process(BP)entries,98 cell composition(CC)entries,and 250 molecular function(MF)entries,mainly involved in inflammatory response,extracellular matrix decomposition,enzyme binding,and steroid hormone receptor activity;149 signal pathways were obtained by KEGG pathway enrichment screening,mainly involving Toll-like receptor signaling pathway,cancer,tumor necrosis factor,hypoxia-inducible factor-1 signaling pathway,phosphatidylinositol 3 kinase/protein kinase B(PI3K/Akt)and so on.Conclusion Modified Xuemaitong No.2 Granules may treat AS through its active components such as ursolic acid and sitosterol by regulating inflammatory response,apoptosis,oxidative stress and other pathways through multiple targets such as MAPK1,MAPK3,MAPK8,IL-6,TNF,MMP2,MMP9.

关 键 词：动脉粥样硬化 加味血脉通2号颗粒 网络药理学 作用机制 

分 类 号：R285.6[医药卫生—中药学] R259.435[医药卫生—中医学]