基于网络药理学与分子对接技术探讨滋肾养血活血汤治疗胚胎反复种植失败作用机制

目的：通过网络药理学和分子对接技术探讨滋肾养血活血汤治疗胚胎反复种植失败（RIF） 的作用机制。方法：利用中药系统药理数据库和分析平台（TCMSP） 查找滋肾养血活血汤组成药物的化学成分，并筛选出有效活性成分及有效活性成分的作用靶点，通过GeneCards和人类在线孟德尔遗传（OMIM） 数据库筛选RIF疾病靶点，将药物有效活性成分作用靶点与RIF疾病靶点取交集，借助String平台制作蛋白质-蛋白质互作（PPI)网络，然后利用Cytoscape3.9.1软件进行网络结构的拓扑分析筛选核心靶点，并构建中药-活性成分-靶点可视化网络图，利用DAVID在线数据库对核心靶点进行富集分析，采用AutoDock Vina软件对筛选出的主要药物有效活性成分和疾病关键靶点进行分子对接验证。结果：共获得122个药物有效活性成分和256个药物作用靶点，疾病相关靶点2 215个，药物-疾病核心靶点36个。经筛选获得5个主要药物有效活性成分与9个疾病关键靶点。京都基因与基因组百科全书（KEGG） 富集分析结果显示，滋肾养血活血汤治疗RIF可能主要通过调控缺氧诱导因子-1（HIF-1）、肿瘤坏死因子（TNF）、丝裂原活化蛋白激酶（MAPK） 等多种信号通路发挥治疗作用。分子对接结果表明，β-谷甾醇与蛋白激酶B1（AKT1）、丹参酮ⅡA与HIF-1A、丹参酮ⅡA与TNF、槲皮素与HIF-1A对接活性较好。结论：滋肾养血活血汤可能通过槲皮素、山柰酚、木犀草素、β-谷甾醇、丹参酮ⅡA等与靶蛋白相互结合，调控多种信号通路发挥治疗RIF的作用。

Exploration on Mechanism of Zishen Yangxue Huoxue Decoction in TreatingRecurrent Implantation Failure Based on Network Pharmacology and MolecularDocking Technology

Abstract： Objective： To discuss the mechanism of Zishen Yangxue Huoxue Decoction in treatingrecurrent implantation failure (RIF) based on network pharmacology and molecular docking technology.Methods： The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) was applied to search for the chemical components of Zishen Yangxue Huoxue Decoction，and toscreen for the effective active ingredients and their targets. The RIF disease targets were screened out byGeneCards and Online Mendelian Inheritance in Man (OMIM)， and the corresponding targets of theeffective active ingredients of the drug were intersected with the RIF disease targets. The String platformwas applied to create a protein-protein interaction (PPI) network， and then the Cytoscape 3.9.1 softwarewas used to perform topological analysis of the network structure to screen for core targets，and a visualnetwork diagram of “Chinese medicinals-active ingredients-targets” was constructed. The DAVID onlinedatabase was used to enrich and analyze the core targets，and AutoDock Vina software was used to verifythe molecular docking of the screened drug active ingredients and disease key targets. Results：A total of122 active ingredients and 256 drug targets were obtained， including 2 215 disease-related targets and36 drug-disease core targets. After screening， 5 main effective active ingredients and 9 key diseasetargets were obtained. The enrichment analysis results of Kyoto Encyclopedia of Genes and Genomes(KEGG) showed that the treatment of RIF with Zishen Yangxue Huoxue Decoction may mainly exert curativeeffects by regulating multiple signaling pathways such as hypoxia inducible factor-1 (HIF-1)， tumornecrosis factor (TNF)， and mitogen activated protein kinase (MAPK). The molecular docking resultsindicated that the docking activity of β-sitosterol and protein kinase B (AKT1)，tanshinone ⅡA and HIF-1A，tanshinone ⅡA and TNF， as well as quercetin and HIF-1A was relatively good. Conclusion： The ZishenYangxue Huoxue Decoction may be processed through the combination of quercetin， kaempferol， andluteolin，β-sitosterol，and tanshinone IIA，and target proteins，to regulate multiple signaling pathways toexert curative effects on RIF.