基于网络药理学和分子对接探寻人参治疗特发性肺间质纤维化的关键靶标及作用机制  

Ginseng in Treating Idiopathic Pulmonary Fibrosis Based on Network Pharmacology and Molecular Docking

作　　者：吕鹏 刘晓明[2] 李芮[2] LV Peng;LIU Xiao-ming;LI Rui(Shandong University of Traditional Chinese Medicine,Jinan 250014,China;Affiliated Hospital of Shandong University of Traditional Chinese Medicine,Jinan 250014,China)

机构地区：[1]山东中医药大学,山东济南250014 [2]山东中医药大学附属医院,山东济南250014

出　　处：《特产研究》2022年第4期59-68,共10页Special Wild Economic Animal and Plant Research

基　　金：山东省中医药管理局山东中医药科技发展计划项目(2019-0088);济南市科学技术局临床医学科技创新计划项目(202019159)。

摘　　要：本研究基于网络药理学与分子对接方法,对人参治疗特发性肺间质纤维化(idiopathic pulmonary fibrosis, IPF)的关键靶标及作用机制进行系统探索。在TCMSP数据库中寻找人参的活性成分与作用靶标;查找NCBI、GeneCards、Disgenet、OMIM和DrugBank疾病数据库得到IPF相关靶标;利用Uniprot数据库将靶标名称转化为Gene symbol;构建PPI网络筛选关键靶标;利用Metascape进行GO和KEGG富集分析;构建生物网络并进行拓扑分析;利用分子对接技术对预测结果进行筛选与验证。结果显示,通过筛选得到TNF、IL1B、PPARG、PTGS2、JUN、IFNG、VCAM1、IL2、HMOX1和NOS2等10个关键靶标,富集的通路有流体切应力与动脉粥样硬化、IL-17信号通路、糖尿病并发症中的AGE-RAGE信号通路及TNF信号通路等20条,功能信息得到649条,包括炎症反应、细胞凋亡和对氧气水平的调节等,在分子对接中表现出较好的抗纤维化潜力的活性成分有人参皂苷Re、人参皂苷Rb1和山柰酚等。人参通过抑制炎症、抑制细胞凋亡、激活细胞自噬和抗氧化应激等生物学过程干预IPF,具体机制可能与人参中的人参皂苷、山柰酚通过Nrf2或IL-17A所在的信号通路介导氧化还原或者细胞自噬过程有关。To obtain the primary targets and mechanisms of ginseng in the therapy of idiopathic pulmonary fibrosis, they were the network pharmacology and molecular docking approaches were used to investigate comprehensively. To find the active components and action targets of ginseng, use the TCMSP database;search a variety of disease databases for IPF-related targets;use the Uniprot database to convert target names into gene symbols;build a PPI network to screen key targets;use Metascape for GO function and KEGG pathway enrichment analysis;build a biological network and topology analysis;use molecular docking technology to screen and validate the prediction results.Results showed: TNF, IL1B, PPARG, PTGS2, JUN, IFNG, VCAM1, IL2, HMOX1 and NOS2 were among the 10 major targets screened.Fluid shear stress and atherosclerosis, IL-17 signal route, AGE-RAGE signal pathway in diabetic complications, TNF signal pathway, and so on were among the enriched pathways. 649 functional data sets were obtained, including inflammatory responses, apoptosis, oxygen level regulation, and so on. It is concluded that ginseng inhibits IPF by biological mechanisms such as inflammation inhibition, apoptosis inhibition, autophagy activation, and oxidative stress. The specific mechanism may be connected to ginsenosides and kaempferol, which are significant active components of ginseng and mediate redox or autophagy via the Nrf2 or IL-17A signal pathway.

关 键 词：网络药理学 分子对接 人参 特发性肺间质纤维化 关键靶标 作用机制 

分 类 号：R285[医药卫生—中药学]