基于网络药理学方法的二至丸治疗肝肾阴虚型崩漏作用机制研究

Mechanism of Erzhi Pills on Liver-kidney Yin Deficiency Metrorrhagia Based on Network Pharmacology

目的筛选二至丸治疗肝肾阴虚型崩漏的主要活性成分,预测其作用的关键靶点及信号通路,建立多成分-多靶点-多通路的网络模型,从分子水平探讨其作用机制。方法通过多个数据库联用检索和文献挖掘,筛选二至丸的主要活性成分及其靶点,运用String平台对交集靶点进行蛋白-蛋白相互作用网络分析,利用Cytoscape3.6.1软件构建二至丸成分-靶点-通路网络,进行网络拓扑学分析,并通过生物学信息注释数据库DAVID分析靶点基因功能及信号通路。结果筛选出二至丸主要活性成分10个,主要包括木犀草素、槲皮素、芹菜素和山柰酚等,通过调节STAT3、IL6、TNF和IL4等92个靶点,调控血管内皮生长因子、孕激素介导的卵泡成熟等29条信号转导通路。结论二至丸主要通过影响血管功能、神经-内分泌、糖脂代谢及炎症和免疫,协同发挥止血、调节激素水平、免疫调节等作用。

Objective To screen the main active components of Erzhi Pills for the treatment of liver-kidney yin deficiency metrorrhagia;To predict its key targets and signaling pathways;To establish a multi-component–multi-target–multi-channel network model;To explore its action mechanism at the molecular level.Methods Multiple database and literature mining methods was used to screen the main active components and the targets of Erzhi Pill.String database was used to perform protein-protein interaction network analysis on intersection targets,and then Cytoscape 3.6.1 software was used to construct the component-target-pathway network for network topology analysis.Target gene function and signaling pathway were analyzed through bioinformatics annotation database DAVID.Results There were 10 main active compounds,such as quercetin,luteoline,apigenin and kaempferol,were screened out from Erzhi Pills.Through regulating 92 key targets including STAT3,IL6,TNF and IL4,29 closely metrorrhagia-related signal transduction pathways,such as VEGF pathway,progesterone-mediated oocyte maturation and so on,were regulated.Conclusion Erzhi Pills achieves the function of haemostatic,hormonal regulation and immune regulation by affecting the vascular function,neuroendocrine,glycolipid metabolism,inflammation and immune.