[关键词]
[摘要]
目的 中医药在治疗复发性流产中显示了充分的优势,但中药多重组分与疾病复杂病理机制之间的作用 模式是中药现代研究亟需解决的关键问题。该研究采用数据挖掘、网络药理学、分子对接方法相结合,分析中 医药治疗复发性流产的用药规律及潜在作用机制。方法 检索知网、万方、维普、PubMed 、Web of Science 等数据库自建库以来至 2024 年 3 月的中医药治疗复发性流产的文献,建立方药数据库,运用 IBM SPSS Modeler 18、IBM SPSS Statistics 26 统计软件进行关联规则和系统聚类分析。利用 TCMSP 获得核心药物的活性 成分及靶点信息,通过 GeneCards、OMIM、DrugBank 等数据库获得疾病靶点,将药物靶点与疾病靶点的交集 作为潜在作用靶点。进行 PPI 网络分析、GO 和 KEGG 富集分析,以阐明其潜在的机制,并进行分子对接。 结果 最终纳入文献 208 篇,得到有效处方 183 个,挖掘出高频核心药物为菟丝子、续断、白术、白芍、桑寄 生、党参、当归,得到交集靶点共 144 个,筛选出的核心活性成分为槲皮素、木犀草素、山柰酚、β-谷甾醇 和 7-甲氧基-2-甲基异黄酮。治疗复发性流产的关键靶点涉及 AKT1、IL-6、TNF、TP53 和 IL-1B。KEGG 富 集分析表明靶点可能通过 TNF、p53、PI3K-AKT 信号通路等调控发挥作用。分子对接结果表明核心活性成分 与关键靶点的对接能量均小于 0 kcal·mol-1 ,对接构象稳定。结论 通过数据挖掘获得中医药治疗复发性流产 的核心药物包括菟丝子、续断、白术等,发挥补益肝肾,益气健脾,行气化痰之效。网络药理学分析显示其作 用机制主要参与炎症反应、免疫调节等生物学过程,通过多靶点、多通路、多途径的治疗特点发挥治疗作用, 可为中医药治疗复发性流产提供理论依据,为进一步发掘其潜在作用机制提供研究方向。
[Key word]
[Abstract]
Objective Traditional Chinese medicine (TCM) has demonstrated significant advantages in treating recurrent spontaneous abortion (RSA). However,the interaction patterns between the multi-component nature of TCM and the complex pathological mechanisms of the disease remain a critical issue in modern TCM research. This study integrates data mining,network pharmacology,and molecular docking methods to analyze the medication patterns and potential mechanisms of TCM in treating RSA. Methods Literature on TCM treatment of RSA was retrieved from CNKI,Wanfang, VIP, PubMed, and Web of Science from their inception to March 2024. A prescription database was established,and association rule mining and systematic cluster analysis were performed using IBM SPSS Modeler 18 and IBM SPSS Statistics 26. Active components and target information of core herbs were obtained from the TCMSP database, while disease targets were retrieved from GeneCards, OMIM, and DrugBank. The intersection of herb targets and disease targets was identified as potential therapeutic targets. Protein-protein interaction (PPI) network analysis, GO functional enrichment, and KEGG pathway analysis were conducted to elucidate the underlying mechanisms, followed by molecular docking. Results A total of 208 articles were included, yielding 183 effective prescriptions. High-frequency core herbs included Cuscutae Semen, Dipsaci Radix, Atractylodis Macrocephalae Rhizoma,Paeoniae Radix Alba,Taxilli Herba,Codonopsis Radix,Angelicae Sinensis Radix. A total of 144 intersection targets were identified,with core active components including quercetin,luteolin,kaempferol,β-sitosterol,and 7-methoxy-2-methylisoflavone. Key targets for RSA treatment involved AKT1, IL-6, TNF, TP53, and IL-1B. KEGG enrichment analysis indicated that these targets may function through pathways such as TNF, p53, and PI3K-AKT signaling. Molecular docking results showed that the docking energies of core active components with key targets were all less than 0 kcal·mol-1 , indicating stable docking conformations. Conclusion Through data mining, core herbs for TCM treatment of RSA, including Cuscutae Semen, Dipsaci Radix, Atractylodis Macrocephalae Rhizoma,were identified. These herbs exert effects by tonifying the liver and kidney,replenishing qi,strengthening the spleen,and resolving phlegm. Network pharmacology revealed that their mechanisms primarily involve biological processes such as inflammatory response and immune regulation,exhibiting multi-target,multi-pathway,and multiapproach therapeutic characteristics. This study provides a theoretical basis for TCM treatment of RSA and offers directions for further exploration of its potential mechanisms.
[中图分类号]
R285.6
[基金项目]
国家自然科学基金面上项目(8217150728)