基于数据挖掘、网络药理学及分子对接技术探讨中医药治疗慢性乙型肝炎肝纤维化的用药规律及机制研究

Exploration on Prescription Rules and Mechanisms of TCM for CHB-Related Liver Fibrosis via Data Mining, Network Pharmacology and Molecular Docking

摘要: 目的：基于数据挖掘、网络药理学及分子对接方法，探究中医药治疗慢性乙型肝炎肝纤维化的核心中药、活性成分及潜在分子机制。方法：检索CNKI、万方、VIP数据库(2000.01~2024.04)，筛选符合纳入标准的方剂，进行频次统计、关联规则及聚类分析以确定核心药物。通过TCMSP、HERB等数据库获取核心药物活性成分及靶点，与疾病靶点(DrugBank, GeneCards, OMIM)取交集，构建PPI网络，进行GO/KEGG富集分析，并开展分子对接验证。结果：共纳入129首方剂，筛选出丹参、黄芪、鳖甲、当归、柴胡、郁金、赤芍、川芎8味核心药物。网络药理学获得135个活性成分，326个交集靶点，关键靶点涉及SRC、STAT3、PIK3R1等。KEGG富集主要涉及PI3K-Akt、MAPK等信号通路。分子对接显示鞣花酸、山奈酚、槲皮素等成分与核心靶点结合能均<−5 kcal·mol⁻¹。结论：该核心组方通过多成分、多靶点、多通路(如PI3K-Akt/MAPK)调控炎症、细胞增殖及磷酸化信号级联，从而发挥抗肝纤维化作用。

Abstract: Objective: To investigate the core traditional Chinese medicines (TCMs), active components, and potential molecular mechanisms in the treatment of chronic hepatitis B (CHB)-related liver fibrosis using data mining, network pharmacology, and molecular docking approaches. Methods: Prescriptions for CHB liver fibrosis were retrieved from CNKI, Wanfang, and VIP databases (January 2000 to April 2024) according to inclusion/exclusion criteria. Frequency analysis, association rule mining, and cluster analysis were performed to identify core TCMs. Active components and corresponding targets of core TCMs were obtained from TCMSP, HERB, and other databases. Disease targets for “Chronic Hepatitis B Liver Fibrosis” were collected from DrugBank, GeneCards, and OMIM. Intersection targets were used to construct a protein-protein interaction (PPI) network, followed by GO functional and KEGG pathway enrichment analyses. Finally, molecular docking was conducted to validate the binding affinities between core components and key targets. Results: A total of 129 valid prescriptions were included. Eight core TCMs were identified: Salvia miltiorrhiza (Danshen), Astragalus membranaceus (Huangqi), Trionyx sinensis carapace (Biejia), Angelica sinensis (Danggui), Bupleurum chinense (Chaihu), Curcuma aromatica (Yujin), Paeonia lactiflora (Chishao), and Ligusticum chuanxiong (Chuanxiong). Network pharmacology analysis yielded 135 active components and 326 overlapping targets between the core TCMs and the disease. Key targets included SRC, STAT3, PIK3R1, PIK3CA, and HSP90AA1. KEGG enrichment mainly involves signaling pathways such as PI3K-Akt and MAPK. Molecular docking shows that the binding energies of components like ellagic acid, kaempferol, and quercetin to the core targets are all less than −5 kcal·mol⁻¹. Conclusion: This core formula regulates inflammation, cell proliferation, and phosphorylation signal cascades through multiple components, multiple targets, and multiple pathways (such as PI3K-Akt/MAPK), thereby exerting an anti-liver fibrosis effect.