[摘要] 目的 探索邻苯二甲酸丁苄酯（butyl benzyl phthalate，BBP）毒性机制对防治肺纤维化的意义。方法 采用网络毒理学结合分子对接技术，通过PubChem、GeneCards等数据库筛选BBP的作用靶点及肺纤维化相关靶点，利用韦恩图分析交集基因。构建蛋白质–蛋白质相互作用网络筛选核心靶点，并通过基因本体论和京都基因与基因组百科全书富集分析揭示通路机制。最后，利用AutoDock进行分子对接验证核心靶点与BBP的结合模式。结果 共筛选出91个BBP诱导肺纤维化的潜在靶点，其中PTGS2、CYP3A4为核心靶点（结合能分别为–1.84kcal/mol、–1.68kcal/mol）。富集分析表明BBP通过G蛋白偶联受体信号通路、钙信号通路及环腺苷酸信号通路调控纤维化进程。分子对接证实BBP与核心靶点通过氢键和疏水作用稳定结合。结论 通过网络毒理学为BBP诱导肺纤维化的分子机制提供初步见解，PTGS2和CYP3A4可能在BBP诱导肺纤维化中发挥关键作用，为环境毒物与疾病关联的机制探索提供新的方法学参考。

[关键词] 邻苯二甲酸丁苄酯；肺纤维化；网络毒理学；分子对接

[中图分类号] R114" """"[文献标识码] A """""[DOI] 10.3969/j.issn.1673-9701.2025.19.002

Association and potential toxicity analysis of butyl benzyl phthalate with pulmonary fibrosis

ZHOU Xinbei^1，2， LIANG Ningjuan¹， WU Ting¹， YU Dandan¹， JIANG Xiaohan¹， TENG Jingjing¹

1.Institute of Toxicology， Anhui Center for Disease Control and Prevention， Hefei 230601， Anhui， China; 2.Anhui Key Laboratory of Occupational Health， Second People’s Hospital of Anhui Province， Hefei 230041， Anhui， China

[Abstract] Objective To explore the significance of the toxicity mechanism of butyl benzyl phthalate （BBP） in prevention and treatment of pulmonary fibrosis. Methods In this study， we used network toxicology combined with molecular docking technology to screen the targets of BBP and those related to pulmonary fibrosis through PubChem， GeneCards and other databases， and analyzed the intersecting genes by using a Wayne diagram. Protein-protein interaction networks were constructed to screen the core targets， and the pathway mechanisms were revealed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. Finally， molecular docking using AutoDock was performed to verify the binding patterns of core targets and BBP. Results A total of 91 potential targets of BBP-induced lung fibrosis were screened， among which PTGS2 and CYP3A4 were the core targets （binding energies of –1.84 kcal/mol and –1.68 kcal/mol， respectively）. Enrichment analysis showed that BBP regulated the fibrosis process through G protein-coupled receptor signaling pathway， calcium signaling pathway and cyclic adenosine monophosphate signaling pathway. Molecular docking confirmed that BBP was stably bound to the core target through hydrogen bonding and hydrophobic interaction. Conclusion This study provides preliminary insights into the molecular mechanism of BBP-induced pulmonary fibrosis through network toxicology， and PTGS2 and CYP3A4 may play key roles in BBP-induced pulmonary fibrosis， which provides a novel reference for the exploration of the mechanism of toxicant-disease association.

[Key words] Butyl benzyl phthalate; Pulmonary fibrosis; Network toxicology; Molecular docking

邻苯二甲酸丁苄酯（butyl benzyl phthalate，BBP）是广泛使用的邻苯二甲酸酯，主要存在于润滑剂、稳定剂、食品包装、家居用品和医疗产品中^[1]。这些物质普遍存在于土壤、沉积物、空气、水和食物中，在自然环境条件下表现出抗降解性，从而对人类新陈代谢、发育、繁殖和行为等基本生物功能构成严重威胁。生物监测研究已成功在不同人群的血液、尿液、精液、脐带血、羊水和母乳中检测到BBP及其代谢物^[2]。研究表明BBP可……