基于“异病同治”理念探讨丹栀逍遥散治疗干眼和抑郁症的网络药理学机制  

Discussion on the Mechanism of Danzhi Xiaoyao Powder in Treating Dry Eye and Depression based on the Concept of"Treating Different Diseases with the Same Treatment"in Network Pharmacology

作　　者：王紫艳 时健 姚小磊[2] 彭清华[1] WANG Ziyan;SHI Jian;YAO Xiaolei;PENG Qinghua(Hunan University of Traditional Chinese Medicine,Hunan Changsha 410208,China;The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine,Hunan Changsha 410021,China)

机构地区：[1]湖南中医药大学,湖南长沙410208 [2]湖南中医药大学第一附属医院,湖南长沙410021

出　　处：《中医药临床杂志》2023年第4期734-743,共10页Clinical Journal of Traditional Chinese Medicine

基　　金：中医药防治眼耳鼻喉疾病湖南省重点实验室开放基金项目(2018YZD02);国家中医药管理局中医眼科学重点学科建设项目(ZK1801YK015);白求恩·朗沐中青年眼科科研基金(BJ-LM2021009J)。

摘　　要：目的:通过网络药理学和分子对接,探讨分析丹栀逍遥散治疗干眼和抑郁的作用机制。方法:通过中药系统药理学数据库与分析平台搜索丹栀逍遥散,结合文献筛选,得到丹栀逍遥散的活性成分和靶点。在DrugBank、Therapeutic Target Database(TTD)、Online MendelianInheritancein Man Database(OMIM)、Gene Cards数据库分别搜索干眼和抑郁,得到干眼和抑郁相关的疾病靶点,运用Cytoscape3.9软件构建“丹栀逍遥散-干眼-抑郁”网络;使用STRING数据库构建靶蛋白相互作用(protein-proteininteraction,PPI)网络;利用R语言对关键靶点进行Gene Ontology(GO)富集和Kyoto EncyclopediaofGenesand Genomes(KEGG)富集分析,研究其作用机制。利用PyMOL和Auto DockVina等软件对丹栀逍遥散活性成分和核心靶蛋白进行分子对接。结果:共收集到丹栀逍遥散药物有效成分3095个以及对应成分靶点2727个;干眼疾病靶点3020个;抑郁疾病靶点3663个;药物与干眼-抑郁的疾病共有靶点132个;最终得到PPI网络肿关键靶点14个,分别为:MYC、HIF1A、ESR1、EGFR、CDKN1A、TP53、FOS、STAT3、MAPK3、STAT1、MAPK14、AKT1、MAPK1、CASP3;GO富集分析得到共2467条,其中细胞组成(cellularcomponent,CC)75条、分子功能(molecularfunction,MF)178条和生物过程(biologicalprocess,BP)2214条。KEGG富集分析得到176条信号通路,主要有:脂质和动脉粥样硬化通路、糖尿病并发症中的AGE-RAGE信号通路、化学致癌-受体激活信号通路、细胞凋亡、内分泌抵抗、TNF信号通路、IL-17信号通路、HIF-1信号通路等信号通路。结论:丹栀逍遥散中的主要成分如槲皮素(quercetin)、柚皮素(naringenin)、木犀草素(luteolin)、芦荟大黄素(aloeemodin)、金合欢素(acacetin)、甘草查尔酮A(licochalcone a)、山奈酚(kaempferol)等,通过脂质和动脉粥样硬化通路、糖尿病并发症中的AGE-RAGE信号通路、化学致癌-受体激活信号通路、细胞凋亡、内分泌抵抗、TNF信号�Objective:To discuss and analyze the mechanism of Danzhi Xiaoyao Powder in treating dry eye and depression through network pharmacology and molecular docking.Methods:The systemic pharmacology database and analysis platform of traditional Chinese medicine were used to search Danzhi Xiaoyao Powder,combined with literature screening,the active ingredients and targets of Danzhi Xiaoyao Powder were obtained.Dry eye and depression were searched in DrugBank,Thera peutic Target Database(TTD),Online Mendelian Inheritancein Man Database(OMIM)and Gene Cards database respectively,and the disease targets related to dry eye and depression were obtained.Cytoscape3.9 software was used to construct“Danzhi Xiaoyao San-Dry Eye-Depression”network;use the STRING database to build a target protein interaction(protein-protein interaction,PPI)network;use R language to enrich the key targets by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)Set analysis to study its mechanism of action.Molecular docking of active ingredients and core target proteins of Danzhi Xiaoyao Powder was carried out by using software such as PyMOL and Auto DockVina.Results:A total of 3095 active ingredients of Danzhi Xiaoyao Powder and 2727 corresponding component targets were collected;3020 targets for dry eye diseases;3663 targets for depression diseases;132 targets for drugs and dry eye-depression diseases;Finally,14 key targets of PPI network were obtained,namely:MYC,HIF1A,ESR1,EGFR,CDKN1A,TP53,FOS,STAT3,MAPK3,STAT1,MAPK14,AKT1,MAPK1,CASP3;GO enrichment analysis obtained a total of 2467 There are 75 pieces of cellular components(CC),178 pieces of molecular function(MF)and 2214 pieces of biological process(BP).KEGG enrichment analysis obtained 176 signaling pathways,mainly including:lipid and atherosclerosis pathway,AGE-RAGE signaling pathway in diabetic complications,chemical carcinogenesis-receptor activation signaling pathway,apoptosis,endocrine resistance,TNF Signaling pathway,IL-17 signaling pathway,HIF-1 signaling pathway and other

关 键 词：丹栀逍遥散 干眼 抑郁 网络药理学 作用机制 

分 类 号：R276.7[医药卫生—中医五官科学]