基于网络毒理学和分子对接技术探讨双酚F对干眼症的作用机制

Investigating the Mechanism of Bisphenol F in Dry Eye Based on Network Toxicology and Molecular Docking

摘要: 目的：应用网络毒理学结合分子对接技术探讨双酚F (Bisphenol F, BPF)促进干眼症(Dry Eye Disease, DED)发生的潜在作用机制。方法：通过Swiss Target Prediction和ChEMBL数据库预测作用靶点。通过GeneCards和OMIM数据库检索干眼症相关靶点。将交集靶点导入STRING数据库构建蛋白质相互作用(PPI)网络，并利用Cytoscape软件进行可视化及拓扑参数分析以筛选核心靶点。使用R语言进行基因本体(GO)功能富集分析和京都基因与基因组百科全书(KEGG)通路分析。最后，利用AutoDock Vina软件对核心靶点与BPF进行分子对接验证。结果：网络毒理学分析共筛选出BPF与干眼症的共有交集靶点26个。网络拓扑分析显示，MMP9和BCL2是BPF促进干眼症最关键的核心靶点。GO分析共获得645个细胞生物学过程，主要涉及细胞凋亡信号的调节、细胞对氧化应激的反应以及氧化还原酶活性等。KEGG富集分析识别出26条相关通路，主要包括NF-κB、IL-17及细胞凋亡信号通路。分子对接结果显示，BPF与核心靶点MMP9和BCL2均具有良好的结合稳定性，其结合能分别为−8.3 kJ/mol和−5.6 kJ/mol。结论：本研究初步揭示了BPF可能通过作用于MMP9、BCL2等靶点，调控NF-κB、IL-17及细胞凋亡等信号通路，诱发眼表炎症反应与氧化还原失衡，从而促进干眼症的发生与发展。这些发现为评估环境干扰物相关的眼部健康风险提供了理论基础，但尚需进一步的体内与体外实验验证。

Abstract: Objective: To investigate the potential molecular mechanisms of Bisphenol F (BPF) in promoting the development of Dry Eye Disease (DED) using network toxicology and molecular docking. Methods: Potential targets of BPF were predicted via the Swiss Target Prediction and ChEMBL databases. DED-associated targets were retrieved from the GeneCards and OMIM databases. Overlapping targets were imported into the STRING database to construct a protein-protein interaction (PPI) network, followed by visualization and topological analysis using Cytoscape to identify hub targets. Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed using R. Finally, the core target and BPF were validated using AutoDock Vina software. Results: Network toxicology analysis identified 26 overlapping targets between BPF and DED. Topological analysis highlighted MMP9 and BCL2 as the primary hub targets. GO enrichment analysis yielded 645 biological processes, predominantly involving the regulation of apoptotic signaling, cellular response to oxidative stress, and oxidoreductase activity. KEGG analysis identified 26 enriched pathways, including the NF-κB, IL-17, and apoptosis signaling pathways. Molecular docking demonstrated high binding stability between BPF and the hub targets MMP9 and BCL2, with binding energies of −8.3 kJ/mol and −5.6 kJ/mol, respectively. Conclusion: This study suggests that BPF exposure may promote DED progression by targeting MMP9 and BCL2 to modulate the NF-κB, IL-17, and apoptotic pathways, thereby triggering ocular surface inflammation and redox imbalance. These findings provide a theoretical basis for evaluating the ocular health risks associated with environmental disruptors, though further in vivo and in vitro validation is warranted.