基于生物信息学对二至丸治疗卵巢早衰的机制研究  

A study on the mechanism of Erzhi Wan in the treatment of premature ovarian failure based on bioinformatics

作　　者：张思敏 刘慧萍 刘平安 张楚洁 ZHANG Simin

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

出　　处：《中医临床研究》2022年第22期12-17,共6页Clinical Journal Of Chinese Medicine

基　　金：湖南省中医药科研计划项目重点项目(2021025);湖南中医药大学校级科研基金重点项目(2020XJJJ003);湖南中医药大学中西医结合一流学科开放基金项目(2020ZXYJH66,2020ZXYJH71);湖南省教育厅科学研究重点项目(21A0233)。

摘　　要：目的:探讨二至丸治疗卵巢早衰的生物信息学作用及分子机制。方法:运用中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)筛选二至丸的潜在活性化合物及靶点蛋白,在蛋白质数据库(Uniprot)中进行基因转换,借助人类孟德尔遗传数据库(OMIM)、人类基因数据库(Gene Cards)检索与卵巢早衰相关的基因,导入Cytoscape 3.6.1软件构建“成分-基因-疾病”网络图,采用蛋白质相互作用数据库(String)构建蛋白质-蛋白质相互作用网络,利用“Centi Scape 2.2”功能进行网络拓扑属性分析,筛选出核心靶点,最后进行基因本体论(GO)基因分析和京都基因与基因组百科全书(KEGG)代谢通路富集分析。结果:共检索出二至丸17种潜在活性化合物和204个相应靶基因,以及4 591个卵巢早衰相关靶基因,通过Cytoscape 3.6.1软件进行网络构建,共获得13种与疾病相关的活性成分及154个靶点基因,结合蛋白质-蛋白质相互作用网络图,二至丸主要参与细胞自噬、细胞增殖、细胞凋亡、细胞代谢等生命过程,通过调控核因子-3(RELA)、丝裂原活化蛋白激酶1(Mitogen-activated Protein Kinase 1,MAPK1)、肿瘤蛋白P53(Tumor Protein P53,TP53)、转化生长因子-β1(Transforming Growth Factor-β1,TGF-β1)、肿瘤坏死因子(Tumor Necrosis Factor,TNF)、白细胞介素-6(Interleukin 6,IL-6)、B细胞κ轻肽基因增强子核因子抑制因子α(NF-κB Inhibitor Alpha,NFKBIA)等靶点发挥治疗卵巢早衰的作用。结论:二至丸可多成分、多靶点、多途径发挥治疗卵巢早衰的作用,这为实验室及临床进一步探究药对治疗卵巢早衰的作用机制提供了一定依据。Objective:To investigate the bioinformatics effect and molecular mechanism of Erzhi Wan(二至丸)in the treatment of premature ovarian failure.Methods:The potential active compounds and target proteins of Erzhi Wan were screened by TCMSP,and then gene conversion was performed in the Uniprot database.The genes related to premature ovarian failure were searched by OMIM and GeneCards databases,and then were imported into the Cytoscape 3.6.1 software in order to construct a“component-gene-disease”network diagram.The String database was used to construct a PPI network diagram,and CentiScape 2.2 function module was used to perform a network topology attribute analysis.The core targets were screened out,and the GO gene analysis and the KEGG metabolic pathway enrichment analysis were performed finally.Results:A total of 17 potential active compounds and 204 corresponding target genes of Erzhi Wan were retrieved,as well as 4591 premature ovarian failure-related target genes.The results of network construction showed that a total of 13 disease-related active ingredients and 154 target genes were obtained.Combined with PPI network diagram,Erzhi Wan is mainly involved in the life process such as cell autophagy,cell proliferation,cell apoptosis,cell metabolism,etc.,and played a role in the treatment of premature ovarian failure by regulating RELA,MAPK1,TP53,TGF-β1,TNF,IL-6,NFKBIA and other targets.Conclusion:The effect of Erzhi Wan in the treatment of premature ovarian failure is multi-component,multi-target,and multi-channel,which provides a basis for the laboratory and clinical research on the mechanism of medicine pair on premature ovarian failure.

关 键 词：卵巢早衰 二至丸 女贞子-旱莲草 生物信息学 网络药理学 

分 类 号：R271.9[医药卫生—中西医结合]