运用网络药理学和分子对接探究山药-陈皮治疗孤独症谱系障碍的机制  

Pair of Chinese Yam and Tangerine Peel in Treating Autism Spectrum Disorder Based on Network Pharmacology and Molecular Docking

作　　者：吴静静 王俊宏[1] 刘玲佳[1] WU Jingjing;WANG Junhong;LIU Lingjia(Beijinf Dongzhimen Hospital,Beijing University of Chinese Medicine,Beijing 100007,China)

机构地区：[1]北京中医药大学东直门医院,北京100007

出　　处：《世界中医药》2021年第18期2696-2701,共6页World Chinese Medicine

基　　金：北京中医药大学青年教师项目(2019-JYB-JS-055);北京中医药大学王俊宏名师工作坊建设项目(MSGZF-201818);北京市教委双一流-中医儿科学资助项目(1000062520566)。

摘　　要：目的:运用网络药理学及分子对接探究山药-陈皮治疗孤独症谱系障碍(ASD)的分子机制。方法:检索中药系统药理学数据库与分析平台(TCMSP)并筛选山药-陈皮活性成分及靶点,检索Genecards、DisGenet、TTD数据库并筛选ASD疾病相关靶点。运用Cytoscape 3.7.2软件建立山药-陈皮靶点基因蛋白质-蛋白质相互作用(PPI)网络及ASD疾病基因PPI网络,提取Hithubs网络,即山药-陈皮治疗ASD的关键靶点。运用DAVID数据库对关键靶点进行基因本体(GO)富集分析和京都基因和基因组百科全书(KEGG)富集分析。运用Autodock软件对山药-陈皮活性成分与关键靶点进行分子对接。结果:筛选山药-陈皮活性成分21个及对应靶点109个,检索ASD相关靶点476个,提取山药-陈皮治疗ASD的关键靶点141个,GO分析结果显示91个生物过程,68个细胞组分和77个分子功能相关过程,KEGG通路富集条目10条(P<0.05)。这些关键靶点涉及rRNA加工、核转录基因分解代谢过程、翻译起始、靶向膜的SRP依赖性共转运蛋白、病毒转录、核糖核酸聚合酶Ⅱ启动子转录正调控、凋亡过程负调控、细胞周期、拼接体、核苷酸切除修复等。分子对接结果显示山药-陈皮活性成分与关键靶点结合构象稳定。结论:山药-陈皮治疗ASD可能通过脑神经网络连接、基因表达、信号转导、炎症反应、病毒转录等途径起效。Objective:To explore the molecular mechanism of Chinese yam and tangerine peel pair in the treatment of autism spectrum disorder on network pharmacology and molecular docking.Methods:TCMSP was used to screen the active components of Chinese yam and tangerine peel pair.Disease targets associated with ASD were retrieved from Genecards、DisGenet and TTD database.The Cytoscape 3.7.2 software was used to construct a drug-compound-target network.Draw Hithubs diagrams for disease targets and drug targets to screen key targets.Further analysis of GO function and KEGG pathway enrichment was conducted by the database for annotation,visualization and integrated discovery(DAVID).Finally,Autodock software was used to conduct molecular docking between drug components and core action targets.Results:A total of 21 active ingredients and 109 potential target genes related to Chinese yam and tangerine peel pair were retrieved from TCMSP.And 476 genes directly related to ASD were obtained from the disease gene database.There were 141 key targets obtained by drawing Hithubs diagrams from component targets and disease targets.GO analysis revealed 91 biological processes,68 cell component expression processes,and 77 molecular function related processes.These genes mainly involved in 10 signaling pathways(P<0.05),such as rRNA processing,nuclear-transcribed mRNA catabolic process,nonsense-mediated decay,translational initiation,SRP-dependent co-translational protein targeting to membrane,viral transcription,positive regulation of transcription from RNA polymeraseⅡpromoter,negative regulation of apoptotic process,cell cycle,spliceosome and nucleotide excision repair.Conclusion:The active ingredients of Chinese yam and tangerine peel pair has active effects on ASD through multi-pathways,including neural network connection,gene expression,signal transduction,inflammatory reaction and viral transcription.

关 键 词：孤独症谱系障碍 山药 陈皮 药对 网络药理学 靶点 信号通路 分子机制 

分 类 号：R285[医药卫生—中药学] R749[医药卫生—中医学]