【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P450对异生素的代谢作 用、趋化因子等信号通路，通过抑制炎症，调节氧化应激，调节类固醇激素生成与代谢等生物学过程发挥对POI的治疗作用。

Objective 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 data of POI in GEO database，then the characteristic expression genes of POI were obtained，and the final POI disease targets were obtained after mapping with POI related targets. Gene Ontology（GO）functional enrichment and Kyoto Encyclopedia of Genes and Genomes（KEGG）pathway enrichment analysis were performed with the help of the Database for Annotation，Visualization，and Integrated Discovery（DAVID）；protein-protein interactions were analyzed using the STRING database；Cytoscape 3.9.1 was used to construct“drug-component-target”to screen the core components and core targets of drugs；finally，MOE2019 molecular docking was used to test the effect correlation 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 biological function analysis contained 92 enrichment results，mainly involving inflammatory response，positive regulation of calcium 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， steroid hormone biosynthesis， chemokines， and other signaling pathways. The results of molecular docking indicated that arachidonate，isorhamnetin and quercetin can be well bined with CYP19A1，ESR2 and PI3K. Conclusion Zishen Yutai Pills play roles in treatment of POI by core components such as arachidonate，isorhamnetin and quercetin through acting on targets such as CYP19A1， ESR2 and PI3K，calcium signaling pathway，ovarian steroid hormone production，cytochrome P450 metabolism of xenobiotics， chemokines and other signaling pathways， and the inhibition of inflammation， regulation of oxidative stress，regulation of steroid hormone production and metabolism and other biological processes and other biological processes.

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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）