基于网络药理学与分子对接探讨甘草干姜汤治疗特发性肺纤维化作用机制  

Research on Mechanism of Gancao Ganjiang Decoction(甘草干姜汤)in Treating Idiopathic Pulmonary Fibrosis Based on Network Pharmacology and Molecular Docking

作　　者：王栋 王晓龙[2] 陈海红 徐梦真 朱庆均[2] WANG Dong;WANG Xiaolong;CHEN Haihong;XU Mengzhen;ZHU Qingjun(Beijing University of Chinese Medicine,Beijing 102488,China;Shandong University of Traditional Chinese Medicine,Jinan 250355,China)

机构地区：[1]北京中医药大学,北京102488 [2]山东中医药大学,山东济南250355

出　　处：《山东中医药大学学报》2022年第3期331-344,共14页Journal of Shandong University of Traditional Chinese Medicine

基　　金：国家自然科学基金面上项目(编号:81774169);国家科技重大专项“重大新药创制”子课题(编号:2014ZX09509001-001);山东省自然科学基金项目(编号:ZR2020MH384)。

摘　　要：目的:基于网络药理学与分子对接探究甘草干姜汤治疗特发性肺纤维化的作用机制。方法:使用多种数据库检索甘草干姜汤化学成分与靶标、特发性肺纤维化疾病靶标,使用Cytoscape 3.7.2软件分别构建成分靶标网络、成分疾病靶标网络、靶标相互作用网络,分析筛选得到关键成分与关键靶标。使用Cytoscape3.7.2软件插件ClueGO对关键靶标进行基因本体论(GO)、京都基因与基因组数据库(KEGG)富集分析,探究甘草干姜汤治疗特发性肺纤维化的潜在作用机制。使用PyRx 0.8软件对关键成分与对应关键靶标进行分子对接,评价配体与受体结合能力。结果:甘草干姜汤中筛选得到34个成分,与治疗特发性肺纤维化相关的靶标591个。网络拓扑分析筛选得到88个关键靶标,KEGG的富集分析结果包括缺氧诱导因子-1(HIF-1)信号通路、磷脂酰肌醇3激酶(PI3K)-蛋白激酶B(Akt)信号通路、叉头盒转录因子O(FoxO)信号通路、肿瘤坏死因子(TNF)信号通路、白细胞介素-17(IL-17)信号通路等145个显著相关通路,涉及调控细胞增殖、迁移、黏附,造血或淋巴器官发育与白细胞分化,调节对外部刺激的反应等966个显著相关生物过程。结论:甘草干姜汤治疗特发性肺纤维化涉及多个重要通路,免疫调节可能为相对重要的作用机制。Objective:To study the mechanism of Gancao Ganjiang Decoction(甘草干姜汤)(GGD)in the treatment of idiopathic pulmonary fibrosis(IPF)based on network pharmacology and molecular docking.Methods:The chemical components and targets of GGD and disease targets of IPF were retrieved from various databases.Cytoscape 3.7.2 software was used to construct the compound target network,compound disease target network,and target interaction network,and to analyze the key compounds and targets.Gene Ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis of key targets were performed using the Cytoscape 3.7.2 software plug-in ClueGO to obtain the potential mechanism of GGD for the treatment of IPF.Molecular docking of key compounds with key targets was performed using PyRx 0.8 software to evaluate the ligand-receptor binding ability.Results:Total 34 compounds were screened in GGD,and 591 targets were associated with the treatment of IPF.The network topology analysis resulted in 88 key targets,and the enrichment analysis of KEGG resulted in 145 significantly pathways including hypoxia inducible factor-1(HIF-1)signaling pathway,phosphatidylinositol 3-hydroxy kinase(PI3K)-protein kinase B(Akt)signaling pathway,forkhead box transcription factor O(FoxO)signaling pathway,tumor necrosis factor(TNF)signaling pathway,interleukin-17(IL-17)signaling pathway,etc.This is associated with 966 significantly related biological processes such as the regulation of cell proliferation,migration,adhesion,hematopoietic or lymphoid organ development and leukocyte differentiation,and the regulation of responses to external stimuli.Conclusions:The treatment of IPF with GGD involves several important pathways,and immunomodulation may be relatively important mechanisms.

关 键 词：甘草干姜汤 特发性肺纤维化 网络药理学 分子对接 信号通路 免疫调节 

分 类 号：R256.15[医药卫生—中医内科学]