基于网络药理学探讨健脾益胃祛邪方治疗大肠癌作用机制  

Mechanism of Jianpi Yiwei Quxie Prescription in Treating Colorectal Cancer Based on Network Pharmacology

作　　者：姜亚君 蔡德珺[1] 梁学敏 朱建红[1] JIANG Yajun;CAI Dejun;LIANG Xuemin;ZHU Jianhong(Zhuhai Branch Hospital of Guangdong Provincial Hospital of Chinese Medicine,Zhuhai Guangdong 519000,China;The Third Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou Guangdong 510145,China)

机构地区：[1]广东省中医院珠海医院,广东珠海519000 [2]广州中医药大学第三附属医院,广东广州510145

出　　处：《新中医》2024年第23期146-153,共8页New Chinese Medicine

基　　金：珠海市医学科研基金项目(12220009000293)。

摘　　要：目的:基于网络药理学研究方法探讨健脾益胃祛邪方治疗大肠癌的作用机制。方法:应用中药系统药理学平台和中药分子机制生物信息学分析工具筛选健脾益胃祛邪方的活性成分及其靶点。利用药物靶标数据库、比较毒理基因组学数据库、在线人类孟德尔遗传数据库以及GeneCards数据库检索大肠癌的靶点。通过Venny2.1平台得出健脾益胃祛邪方和大肠癌的共同靶点,绘制韦恩图。将健脾益胃祛邪方与大肠癌的共同靶点录入STRING数据库中进行分析,构建大肠癌和健脾益胃祛邪方的蛋白质-蛋白质相互作用(PPI)网络。借助DAVID数据库,对健脾益胃祛邪方与大肠癌的共同靶点进行基因本体(GO)功能富集分析以及京都基因与基因组百科全书(KEGG)通路富集分析。利用Cytoscape3.82软件构建“药物-成分-作用靶点-通路-疾病”网络模型。结果:通过筛选,得到126个健脾益胃祛邪方的主要活性成分,1014个与大肠癌相关的人类靶点,59个健脾益胃祛邪方与大肠癌的共同靶点。PPI网络分析提示前列腺素内过氧化物合酶1、核受体辅活化因子2、雄激素受体、热休克蛋白90α、雌激素受体1、胰蛋白酶-1、过氧化物酶体增殖物激活受体γ、丝氨酸/苏氨酸激酶β、雌激素受体2、丝氨酸/苏氨酸蛋白激酶Chk1是健脾益胃祛邪方治疗大肠癌的核心靶点。GO功能富集分析得到1133项生物过程条目,93项分子功能条目,27项细胞组分条目;KEGG通路富集分析共得到140条信号通路。健脾益胃祛邪方的主要活性成分如槲皮素、山奈酚、木犀草素、汉黄芩素等,通过靶向调控机制与化学致癌-受体激活、细胞凋亡、结直肠癌、p53信号通路、人巨细胞病毒感染以及内分泌抵抗等信号通路,发挥治疗大肠癌的作用。结论:健脾益胃祛邪方治疗大肠癌具有多成分、多靶点、多通路的特点。Objective:To explore the mechanism of Jianpi Yiwei Quxie Prescription in the treatment of colorectal cancer based on network pharmacology.Methods:The active components and targets of Jianpi Yiwei Quxie Prescription were screened by the function of bioinformatics analysis in Traditional Chinese Medicine Systematic Pharmacology Database and Analysis Platform(TCMSP)and A Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine(BATMAN-TCM).The targets of colorectal cancer were searched through Therapeutic Target Database,Comparative Toxicogenomics Database,Online Mendelian Inheritance in Man and GeneCards databases.The common targets of Jianpi Yiwei Quxie Prescription and colorectal cancer were obtained via Venn 2.1,and Venny diagram was drawn.The common targets were analyzed through STRING database,and then the protein-protein interaction(PPI)network of colorectal cancer and Jianpi Yiwei Quxie Prescription was constructed.With the use of David database,Gene Ontology(GO)function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed for the common targets of Jianpi Yiwei Quxie Prescription and colorectal cancer.Cytoscape3.82 software was used to construct a“drug-component-target-pathway-disease”network model.Results:Through screening,126 main active components of Jianpi Yiwei Quxie Prescription,1014 human targets related to colorectal cancer,and 59 common targets of Jianpi Yiwei Quxie Prescription and colorectal cancer were obtained.PPI network analysis showed that prostaglandin-endoperoxide synthase 1,nuclear receptor coactivator 2,androgen receptor,heat shock proteins 90α,estrogen receptor 1,trypsin-1,peroxisome proliferators-activated receptorsγ,receptor serine/threonine kinasesβ,estrogen receptor 2 and checkpoint kinase 1 were the core targets of Jianpi Yiwei Quxie Prescription.A total of 1133 biological process items,93 molecular function items and 27 cellular component items were obtained by GO functional enrichment anal

关 键 词：大肠癌 健脾益胃祛邪方 网络药理学 作用机制 富集分析 信号通路 

分 类 号：R285[医药卫生—中药学]