基于网络药理学及分子对接技术探讨小承气汤治疗急性胰腺炎机制的研究  

To investigate the mechanism of Xiaochengqi decoction in the treatment of acute pancreatitis based on network pharmacology andmolecular docking

作　　者：王恺 王琳 于勇 张汝敏[1] 侯念宗[2] Wang Kai;Wang Lin;Yu Yong;Zhang Rumin;Hou Nianzong(Department of Critical Care Medicine,Zibo Central Hospital,Shandong First Medical University&Shandong Academy of Medical Sciences,Zibo 255036,Shandong,China;Centre for Translational Medicine,Zibo Central Hospital,Shandong First Medical University&Shandong Academy of Medical Sciences,Zibo 255036,Shandong,China)

机构地区：[1]山东第一医科大学附属淄博市中心医院重症医学科,山东淄博255036 [2]山东第一医科大学附属淄博市中心医院转化医学中心,山东淄博255036

出　　处：《中国中西医结合急救杂志》2023年第5期568-575,共8页Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care

基　　金：山东省淄博市重点研发计划(2020ZC010048);山东省医药卫生科技发展计划(202010000131,202104070065)。

摘　　要：目的应用网络药理学与分子对接技术探讨小承气汤治疗急性胰腺炎(AP)的作用机制.方法于中药药理学分析平台(TCMSP)数据库筛选大黄、枳实、厚朴的活性成分,应用瑞士目标预测(STP)数据库预测相关靶点.通过药物银行(DrugBank)数据库、基因卡片(GeneCards)数据库、人类孟德尔遗传在线(OMIM)数据库、治疗靶点数据库(TTD)及药物基因组学知识库(PharmGKB)数据库中筛选出AP的相关靶点.运用String数据库构建靶点蛋白互作网络,采用Cytoscape绘制网络并进行拓扑学分析,使用R3.6.2软件对相关靶点进行基因本体(GO)富集分析和京都基因与基因组百科全书(KEGG)通路注释分析,通过Autodock 4.2.6软件以及Vina软件进行分子对接.结果共筛选出小承气汤与AP直接相关的交集靶点124个,通过网络拓扑分析发现11个靶点,包括视网膜母细胞瘤1(RB1)基因、蛋白激酶B(PKB)基因、细胞周期蛋白D1(CCND1)基因、禽髓细胞瘤病毒癌基因同源物(MYC)基因、雌激素受体1(ESR1)基因、网状内皮细胞过多症病毒癌基因同源物A(RELA)基因、激活蛋白1(AP-1)基因、p53基因、丝裂素活化蛋白激酶(MAPK1、3、14)基因为核心靶点.GO富集分析及KEGG通路富集分析显示,小承气汤可通过干预细胞凋亡、调节胰腺细胞增殖分化、抑制氧化应激等方面治疗AP,其中磷脂酰肌醇3-激酶/蛋白激酶B(PI3K/Akt)信号通路是最重要的通路.选取小承气汤关键活性成分与核心基因靶点进行分子对接,结果表明,柚皮素分别与PKB、MAPK1、MAPK3;川陈皮素分别与AP-1、p53基因;木犀草素分别与CCND1、RB1 RELA;木犀草素四甲醚与MAPK14;芦荟大黄素与MYC;儿茶素与ESR1等11对成分-靶点对接的自由能较小,显示出良好的对接活性.结论通过网络药理及分子对接的方法证实小承气汤治疗AP具有多途径、多靶点作用的特点,并揭示了相关物质基础和作用机制,这为经典名方在临床的广泛�Objective To investigate the mechanism of Xiaochengqi decoction(XCQD)in the treatment of acute pancreatitis(AP)based on network pharmacology and molecular docking.Methods Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)was used to screen the active components of Rhubarb-Trifoliate-Magnolia officinalis and Swiss Target Prediction(STP)to predict the drug targets.The relevant targets of AP were screened in the databases of DrugBank,GeneCards,Online Mendelian Inheritance in Man(OMIM),Therapeutic Target Database(TTD)and Pharmacogenomics Knowledge Base(PharmGKB).The target protein interaction network was constructed by String software,and the network was drawn by Cytoscape and analyzed by topology.respectively.R3.6.2 was used for Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis.Autodock 4.2.6 and Vina were used for molecular docking.Results A total of 124 related therapeutic targets were obtained.Eleven targets,including retinoblastoma 1(RBI),protein kinase B(PKB),cyclin DI(CCMDI),v-myc avian myelocytomatosis viral oncogene homolog(MYC),estrogen receptorl(ESRI),reticuloendotheliosis virus oncogene homolog A(RELA),activator protein-1(AP-1),p53,mitogen-activated protein kinases(MAPK 1,3 and 14),were found to be the core targets by network topology analysis.GO and KECG enrichment analysis showed that XCQD could play a role in the treatment of AP by regulating the apoptosis,proliferation and differentiation of pancreatic cells,inhibiting oxidative stress,etc,among which,phosphatidylinositol 3 kinase-protein kinase B(PI3K-Akt)signaling pathway is the most important one.In terms of molecular docking,Naringenin-MAPK1,Naringenin-MAPK3,Naringenin-PKB,Nobiletin-p53,Nobiletin-AP-1,Luteolin-CCND1,Luteolin-RELA,Tetramethoxyluteolin-MAPK14,Aloe-emodin-MYC and catechin-ESR1 showed good docking activity due to their low free energy.Conclusion By using network pharmacology and molecular docking,it was confirmed that XCQD had the characteristics of multi-channel

关 键 词：小承气汤 急性胰腺炎 网络药理学 分子对接 机制 

分 类 号：R285[医药卫生—中药学] R576[医药卫生—中医学]