基于网络药理学探讨酸枣仁汤治疗睡眠障碍的作用机制

Mechanisms of Suanzaoren decoction in treatment of insomnia disorder based on network pharmacology

目的:基于网络药理学方法分析酸枣仁汤治疗睡眠障碍的相关靶点及通路,以探讨其作用机制。方法:检索中药系统药理学数据库和分析平台(TCMSP),得出酸枣仁、川芎、知母、甘草、茯苓的有效成分及其作用靶点,通过UniProt数据库匹配靶点对应基因,使用CytoscapeV3.7.1构建疾病-成分-靶点网络。利用GeneCards、OMIM、TTD等数据库搜集睡眠障碍相关基因,运行R语言筛选出酸枣仁汤与睡眠障碍的交集基因,输入String数据库,得出蛋白相互作用关系,并应用Metascape数据库进行GO富集分析和KEGG通路富集分析。结果:共筛选出酸枣仁汤有效成分88种,相关靶点82个;与睡眠障碍交集靶点36个,其中核心靶点8个;GO富集分析获得645条结果,集中在神经递质水平调节、肾上腺素受体活性和突触后膜的组成部分等方面;KEGG通路获得相关通路61条,主要集中在神经活性配体-受体相互作用、脂肪细胞中的脂肪分解调节和雌激素信号通路等。结论:初步得出酸枣仁汤多成分、多靶点、多通路治疗睡眠障碍的作用机制,为进一步研究提供理论参考。

Objective:To explore the mechanisms by analyzing the targets and pathways of Suanzaoren decoction in the treatment of insomnia disorder based on network pharmacology.Methods:The effective chemical components and target genes of Semen Ziziphi spinosae,Rhizoma liqustici Chuanxiong,Rhizoma Anemarrhenae,Radix Glycyrrhizae and Poria were collected from TCMSP database,then matched the targets with gene symbols by utilizing UniProt database,and constructed the disease-components-targets network by using Cytoscape V3.7.1.Genes of insomnia disorder were obtained through databases of GeneCards,OMIM and TTD,then intersectional genes of Suanzaoren decoction and insomnia disorder were selected by running R language.These datas were pasted in String database to get protein-protein interactions,then conducted enrichment analysis of Gene Ontology(GO)and KEGG pathway of intersection genes with Metascape online tools.Results:88 effective chemical components,82 gene targets in Suanzaoren decoction were collected in total.There were 36 intersectional target genes with insomnia disorder,8 of them were core targets.645 results were obtained through GO enrichment analysis,involving regulation of neurotransmitter levels,adrenergic receptor activity,integral component of postsynaptic membrane.61 pathways were obtained through KEGG pathway enrichment analysis,including neuroactive ligand-receptor interaction,regulation of lipolysis in adipocytes,estrogen signaling pathway.Conclusion:This study preliminarily acquired the mechanism of multi-component,multi-target and multi-channel of insomnia disorder treated by Suanzaoren decoction,which provided theoretical reference for further research.