基于网络药理学、生信分析和分子对接探讨滋肾育胎丸治疗早发性卵巢功能不全的机制  

Exploring the Mechanism of Zishen Yutai Pills in the Treatment of Premature Ovarian Insufficiency Based on Network Pharmacology,Bioinformatics Analysis and Molecular Docking

作　　者：邹宇馨 朱玲[2] ZOU Yuxin;ZHU Ling(Graduate School of Guangzhou University of Chinese Medicine,Guangzhou 510405 Guangdong,China;The First Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510405 Guangdong,China)

机构地区：[1]广州中医药大学研究生院,广东广州510405 [2]广州中医药大学第一附属医院,广东广州510405

出　　处：《广州中医药大学学报》2025年第2期437-447,共11页Journal of Guangzhou University of Traditional Chinese Medicine

基　　金：国家自然科学基金资助项目(编号:82174418);全国名老中医药专家传承工作室(国中医药人教函[2022]75号);全国名中医工作室(国中医药人教发[2022]5号)。

摘　　要：【目的】联合网络药理学、生物信息分析学、分子对接技术,探究滋肾育胎丸治疗早发性卵巢功能不全(POI)的机制。【方法】通过中药系统药理学数据库与分析平台(TCMSP)、本草组鉴数据库(HERB)、中医药信息数据库(TCM-ID)查询并筛选滋肾育胎丸中中药的活性成分;使用有机小分子生物活性数据库(PubChem)、小分子药物靶点预测在线平台(Swiss Target Prediction)预测药物作用的靶点;运用人类基因数据库(GeneCards)、比较遗传毒理学数据库(CTD)获取POI相关靶点;借助R语言进行差异表达分析(DEGs)及加权基因共表达网络分析(WGCNA)GEO数据库中POI的转录组数据,得到POI的特征表达基因,与POI相关靶点映射后得到最终POI疾病靶点;药物靶点与疾病靶点交集后初步获得药物作用于疾病的靶点;借助注释、可视化和集成发现数据库(DAVID)进行基因本体论(GO)功能富集与京都基因和基因组百科全书(KEGG)通路富集分析;使用STRING数据库进行蛋白质互作分析;使用Cytoscape 3.9.1构建“药物-成分-靶点”筛选药物核心成分及核心靶点;最后利用MOE2019分子对接,检验核心成分与靶点的效应关系。【结果】滋肾育胎丸中共筛选出111个有效成分,核心成分3个,36个作用于POI的靶点,其中核心靶点3个。GO生物功能分析包含92条富集结果,主要涉及炎症反应、正向调节钙信号通路、类固醇激素生成等。KEGG富集得到15条通路,主要包括病毒蛋白与细胞因子及细胞因子受体的相互作用、色氨酸代谢、钙信号通路、卵巢类固醇生成、类固醇激素生物合成、趋化因子等信号通路。分子对接结果显示花生四烯酸、异鼠李素、槲皮素与CYP19A1、ESR2、PI3K均可较好结合。【结论】滋肾育胎丸可能通过花生四烯酸、异鼠李素、槲皮素等核心成分作用于CYP19A1、ESR2、PI3K等靶点,通过钙信号通路、卵巢类固醇激素生成、细胞色素P450Objective To investigate the mechanism of Zishen Yutai Pills in the treatment of premature ovarian insufficiency(POI)by combining network pharmacology,bioinformatics analysis and molecular docking technology.Methods Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),HERB Database and Traditional Chinese Medicines Integrated Database(TCM-ID)were used to search and screen the active ingredients of Zishen Yutai Pills;PubChem and Swiss Target Prediction were used to predict the action targets of drug;Human Gene Database(GeneCards)and Comparative Toxicogenomics Database(CTD)were utilized to obtain the associated targets of POI;differential expression genes(DEGs)and weighted gene co-expression network(WGCNA)were performed with the help of R language to analyze transcriptome dataof POI in GEO database,then the characteristic expression genes of POI were obtained,and the final POI diseasetargets were obtained after mapping with POI related targets.Gene Ontology(GO)functional enrichment and KyotoEncyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed with the help of theDatabase for Annotation,Visualization,and Integrated Discovery(DAVID);protein-protein interactions wereanalyzed using the STRING database;Cytoscape 3.9.1 was used to construct“drug-component-target”to screenthe core components and core targets of drugs;finally,MOE2019 molecular docking was used to test the effectcorrelation between the core components of the drugs and the targets.Results A total of 111 active ingredients,3 core ingredients and 36 POI targets,including 3 core targets,were screened in Zishen Yutai Pills.GO biologicalfunction analysis contained 92 enrichment results,mainly involving inflammatory response,positive regulation ofcalcium signaling pathway,steroid hormone production,etc.,KEGG enrichment obtained 15 pathways,mainly including interaction of viral proteins with cytokines and cytokine receptors,tryptophan metabolism,calcium signaling pathway,ovarian steroidogenesis,ste

关 键 词：滋肾育胎丸 早发性卵巢功能不全 网络药理学 生物信息学分析 分子对接 作用机制 

分 类 号：R285[医药卫生—中药学]