基于网络药理学与分子对接技术探讨黄连素-丹参酮ⅡA抗动脉粥样硬化的作用机制  

The Mechanism of Berberine-TanshinoneⅡA for the Treatment of Atherosclerosis Based on Network Pharmacology and Molecular Docking Technology

作　　者：黄弘博 史大卓[1,3] 王培利 刘剑刚[1,3] 刘宇轩 许琳洁[2,3] 张莹 HUANG Hongbo;SHI Dazhuo;WANG Peili;LIU Jiangang;LIU Yuxuan;XU Linjie;ZHANG Ying(Xiyuan Hospital,China Academy of Chinese Medical Sciences,Beijing 100091,China;Beijing University of Chinese Medicine,Beijing 100029,China;National Clinical Research Center for Chinese Medicine Cardiology,Beijing 100091,China)

机构地区：[1]中国中医科学院西苑医院,北京100091 [2]北京中医药大学,北京100029 [3]国家中医心血管病临床医学研究中心,北京100091

出　　处：《中西医结合心脑血管病杂志》2024年第22期4051-4062,共12页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease

基　　金：中央级公益性科研院所基本科研业务费专项(No.ZZ13-YQ-008);中国中医科学院科技创新工程重大攻关项目(No.CI2021A03115)。

摘　　要：目的:基于网络药理学和分子对接的方法探讨“黄连素-丹参酮ⅡA”抗动脉粥样硬化的潜在靶点和通路,以期为基础研究及临床应用提供依据。方法:通过PubChem数据库获得黄连素-丹参酮ⅡA分子结构及作用靶点,应用SwissTargetPrediction平台预测作用靶点;通过GeneCards、OMIM、DisGeNET数据库检索并筛选动脉粥样硬化的治疗靶点,取药物靶点和疾病靶点的交集;通过STRING 11.5数据库构建蛋白-蛋白互作(PPI)网络,并通过Cytoscape 3.9.1软件进行拓扑分析;通过DAVID数据库对交集靶点进行基因本体(GO)功能富集分析、京都基因和基因组百科全书(KEGG)通路富集分析;采用AutoDock Tools 1.5.6、PyMOL 2.5.5等进行分子对接分析。结果:共获得95个黄连素-丹参酮ⅡA-动脉粥样硬化交集靶点。蛋白质相互作用分析挖掘其有效成分可能作用的核心靶点包括原癌基因酪氨酸蛋白激酶(SRC)、磷脂酰肌醇-3-激酶调节亚基1(PIK3R1)、磷脂酰肌醇-4,5-二磷酸3-激酶催化亚基α(PIK3CA)、细胞分裂周期蛋白42(CDC42)、淋巴细胞特异性蛋白酪氨酸激酶(LCK)、Janus激酶2(JAK2)、Abelson鼠白血病病毒癌基因同源物1(ABL1)、Ras相关C3肉毒杆菌毒素底物1(RAC1)等。GO功能富集分析结果显示,黄连素-丹参酮ⅡA抗动脉粥样硬化主要涉及蛋白质磷酸化、信号转导、对外源刺激的反应、对药物的反应、免疫应答等230条生物功能。KEGG信号通路富集结果显示,黄连素-丹参酮ⅡA抗动脉粥样硬化的潜在作用途径包括脂质与动脉粥样硬化信号通路、神经营养素信号通路、磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(AKT)信号通路、血管内皮生长因子(VEGF)信号通路、丝裂原活化蛋白激酶(MAPK)信号通路、大鼠肉瘤(Ras)信号通路等106条信号通路。将黄连素-丹参酮ⅡA与筛选的8个核心靶点进行分子对接,结合能均<-20.92 kJ/mol,表明关键靶点和黄连素-丹参酮ⅡA结合活性较�Objective:To investigate the potential targets and pathways of"berberine-tanshinoneⅡA"against atherosclerosis by network pharmacology and molecular docking methods.Methods:The molecular structure and targets of berberine-tanshinoneⅡA were obtained from PubChem database,and the targets were predicted by SwissTargetPrediction platform.The therapeutic targets of atherosclerosis were searched and screened through GeneCards,OMIM and DisGeNET databases,and the intersection of drug targets and disease targets was obtained.The protein-protein interaction(PPI)network was constructed by STRING 11.5 database,and the topology was analyzed by Cytoscape 3.9.1 software.The gene ontology(GO)function enrichment analysis and the Kyoto Encyclopedia of Genomes(KEGG)pathway enrichment analysis were performed for the intersection targets through DAVID database.AutoDock Tools 1.5.6 and PyMOL 2.5.5 were used for molecular docking study.Results:A total of 95 intersection targets of berberine-tanshinoneⅡA-atherosclerosis were obtained.The core targets of protein interaction analysis to explore the possible action of active components mainly included proto-oncogene tyrosine protein kinase(SRC),phosphatidylinosito-l 3-kinase regulatory subunit 1(PIK3R1),phosphatidylinosito-l 4,and phosphatidylinosito-l 4,5-diphosphate 3-kinase catalytic subunitα(PIK3CA),cell division cyclin 42(CDC42),lymphocyte specific protein tyrosine kinase(LCK),Janus kinase 2(JAK2),Abelson murine leukemia virus oncogene homology 1(ABL1),and RAS-associated C3 botulinum toxin substrate 1(RAC1).The results of GO functional enrichment analysis showed that the ant-i atherosclerosis of berberine-tanshinoneⅡA mainly involved 230 biological functions,such as protein phosphorylation,signal transduction,response to exogenous stimuli,response to drugs,and immune response.Enrichment results of KEGG signal pathway involved 106 signaling pathways,such as the potential pathways of berberine-tanshinositoneⅡA against atherosclerosis included lipid and atherosclerosis signalin

关 键 词：动脉粥样硬化 黄连素 丹参酮ⅡA 网络药理学 分子对接 作用机制 

分 类 号：R285[医药卫生—中药学]