生殖医学杂志

目的 运用网络药理学进行数据挖掘，探讨金匮肾气丸治疗早发性卵巢功能不全(POI)的作用机制。方法 从中药系统药理学分析平台(TCMSP)筛选金匮肾气丸的活性成分，从SwissTargetPrediction、SEA数据库中对金匮肾气丸的活性成分进行靶标预测，并与从Drugbank、GeneCards、OMIM中检索的POI相关靶点进行对比分析，取交集后得到金匮肾气丸治疗POI的潜在靶点。使用STRING构建蛋白质相互作用网络，使用cytoscape3.7.2软件构建金匮肾气丸各药材-活性成分-潜在靶点网络，使用Metascape数据库对潜在靶点进行京都基因与基因组百科全书(KEGG)和基因本体论(GO)富集分析，并利用Autodock软件进行核心成分和核心靶点的分子对接验证。结果 在TCMSP数据库中共检索出金匮肾气丸活性成分102个，在SwissTargetPrediction、SEA数据库中共预测出金匮肾气丸潜在靶点432个，整理取交集后得到金匮肾气丸治疗POI的潜在靶点82个。潜在靶点进行GO和KEGG富集后得到1 805条GO条目，主要富集在正向调整激酶活性、腺体发育、受体复合物、蛋白激酶活性等方面；263条KEGG条目，主要富集在磷脂酰肌醇3-激酶/蛋白激酶B(PI3K-Akt)、丝裂原活化蛋白激酶(MAPK)、缺氧诱导因子-1(HIF-1)等信号通路上。分子对接结果显示薯蓣皂苷元与雌激素受体α(ESR1)、血管内皮生长因子A(VEGFA)、丝氨酸苏氨酸蛋白激酶(AKT1),泽泻醇B与ESR1、AKT1,羟基芫花素与ESR1,胡椒碱和ESR1具有较强的结合力。结论 金匮肾气丸可能通过介导细胞增殖和分化、衰老与凋亡，通过抗炎、抗氧化及调节激素的合成与分泌等机制发挥对POI的治疗作用。

Objective:To explore the mechanism of Jingui Shenqi pills in treatment of premature ovarian insufficiency(POI) by using network pharmacology for data mining.Methods:The active components of Jingui Shenqi pills were screened from pharmacological analysis of Traditional Chinese Medicine System Platform(TCMSP). The targets of active components of Jingui Shenqi pills were predicted from SwissTargetPrediction and SEA databases, and compared with the POI related targets retrieved from Drugbank, GeneCards and OMIM. The potential targets of Jingui Shenqi pills for treatment of POI were obtained after intersection. The protein interaction network was constructed with STRING,and the network of various medicinal materials-active components-potential targets was constructed with cytoscape3.7.2 software. The enrichment analysis of Kyoto Encyclopedia of Genes and Genomes(KEGG) and Gene Ontology(GO) for potential targets was performed with Metascape database. Autodock software was used for verifying molecular docking of core compounds and core targets.Results:A total of 102 active components of Jingui Shenqi pills were screened by TCMSP database, and 432 potential targets of Jingui Shenqi pills were predicted by using SwissTargetPrediction and SEA databases. Eighty-two potential targets of Jingui Shenqi pills for treatment of POI were obtained after intersection. After enrichment of potential targets with GO and KEGG,1 805 GO items were obtained, which mainly enriched in positive regulating kinase activity, gland development, receptor complex and protein kinase activity, and 263 KEGG items were mainly enriched in the signaling pathways of phosphatidylinositol 3-kinase/protein kinase B(PI3 K-Akt),mitogen activated protein kinase(MAPK) and hypoxia inducible factor-1(HIF-1). Molecular docking results showed that diosgenin had strong binding ability with estrogen receptor α(ESR1),vascular endothelial growth factor A(VEGFA),serine threonine protein kinase(AKT1). Alisol B had strong binding ability with ESR1 and AKT1,hydroxygenkwanin with ESR1,and piperine with ESR1.Conclusions:Jingui Shenqi pills treat POI by the mechanism of mediating cell proliferation & differentiation, senescence & apoptosis, anti-inflammation, anti-oxidation and regulating hormone synthesis and secretion.