吴静静　王俊宏　刘玲佳　

摘要 目的：運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。

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

Abstract 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 polymerase Ⅱ promoter，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.

Keywords Autism spectrum disorder; Chinese yam; Tangerine peel; pair medicinal; Network pharmacology; Target; Signaling pathway; Molecular mechanism

中图分类号：R285;R749文献标识码：Adoi：10.3969/j.issn.1673-7202.2021.18.007

孤独症谱系障碍（Autism Spectrum Disorder，ASD），是以社会交往障碍、语言交流障碍、重复刻板行为及兴趣狭窄为特征的精神发育障碍性疾病[1]，多发病于婴幼儿。近年来该病患病率逐年升高，在发达国家，ASD患病率已达1.5%[2]。ASD病因复杂，发病机制尚不明确，可能与环境因素、遗传因素等相关。对本病的治疗，尚无明确有效的治疗方案，以教育干预为主，以对症药物治疗为辅，预后不佳[3]。ASD常伴一种或多种共患病，如智力损害、焦虑障碍、结构性语言障碍、癫痫、注意缺陷多动障碍、睡眠障碍等，此外，有研究显……