通讯作者: 滕晶晶, tjj@ahcdc.com.cn

DOI：10.12201/bmr.202504.00004

Effective exploration of the toxicity and molecular mechanisms of plasticisers in pulmonary fibrosis by network toxicology and molecular docking strategies: an example of butylbenzyl phthalate

• 摘要：背景：邻苯二甲酸丁苄酯（BBP）是一种广泛使用的增塑剂，因其显著的耐降解性而具有环境持久性。最近的研究证实，暴露于BBP 与肺功能减退和肺纤维化的发展之间存相关性。这种顽固性疾病的特点是死亡率高，且缺乏有效的治疗方法，因此有必要探索其毒性作用的机制。方法：本研究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（PPI）网络，筛选核心靶点，并通过基因本体（GO）和京都基因与基因组百科全书（KEGG）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和TRPV1为核心靶点（结合能分别为-1.84、-1.68和0.56 kcal/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cAMP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：本研究首次通过网络毒理学揭示BBP诱导肺纤维化的分子机制，明确了PTGS2和CYP3A4的关键作用及信号通路网络，为靶向治疗和药物开发提供理论依据。该研究为环境毒物与疾病关联的机制探索提供了新方法学参考。

  关键词： 邻苯二甲酸丁苄酯; 肺纤维化; 网络毒理学; 分子对接

   

  Abstract: Background: Butylbenzyl phthalate (BBP) is a widely used plasticiser that is environmentally persistent due to its remarkable resistance to degradation. Recent studies have confirmed the correlation between BBP exposure and the development of reduced lung function and pulmonary fibrosis. This persistent disease is characterised by a high mortality rate and a lack of effective treatments, making it necessary to explore the mechanisms of its toxic effects.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 analysed the intersecting genes by using a Wayne diagram. Protein-protein interaction (PPI) networks were constructed to screen the core targets, and the pathway mechanisms were revealed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Finally, molecular docking using AutoDock was performed to verify the binding patterns of the core targets and BBPs.Results: A total of 91 potential targets of BBP-induced pulmonary fibrosis were screened, among which PTGS2, CYP3A4 and TRPV1 were the core targets (binding energies of -1.84, -1.68 and 0.56 kcal/mol, respectively). Enrichment analysis showed that BBP regulated fibrosis progression through G protein-coupled receptor signalling pathway, calcium signalling pathway and cAMP signalling pathway. Molecular docking confirmed that BBP was stably bound to the core target through hydrogen bonding and hydrophobic interaction.Conclusion: This study is the first to reveal the molecular mechanism of BBP-induced lung fibrosis through network toxicology, clarifying the key roles of PTGS2 and CYP3A4 and the signalling pathway network, and providing a theoretical basis for targeted therapy and drug development. This study provides a new methodological reference for the exploration of the mechanism of the association between environmental toxicants and diseases.

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

  提交时间：2025-04-02

  版权声明：作者本人独立拥有该论文的版权，预印本系统仅拥有论文的永久保存权利。任何人未经允许不得重复使用。
• html

• 图表

• 张家芮, 杜雨芃, 林燕. 特发性腹膜后纤维化2例诊治经验探讨. 2024. doi: 10.12201/bmr.202410.00077

  洪天琪, 杨笑亚, 张慧燕, 葛凯莉, 薛洋洋, 魏春山. 基于数据挖掘和网络药理学探析肝癌的用药规律及作用机制. 2024. doi: 10.12201/bmr.202407.00040

  李雪雪, 赵粉琴. 卵巢纤维化发生机制及相关疾病研究进展. 2025. doi: 10.12201/bmr.202501.00040

  钱蒙蒙, 郭潇辰, 王鹏飞, 陈秀, 伍欣尧, 邹春鹏, 徐茂晟. SWE在MAFLD早期肝脏及肾脏纤维化中的应用价值. 2024. doi: 10.12201/bmr.202409.00010

  卢一帆, 袁拯忠. 基于网络药理学探讨交泰丸治疗失眠作用机制. 2024. doi: 10.12201/bmr.202408.00069

  汪满满, 杭于洁, 陈坤, 刘千羽, 章钰斌, 许亮, 张立雪, 白静雅▲. 肾脏纤维化生物标志物的研究进展. 2024. doi: 10.12201/bmr.202411.00072

  段嘉敏, 蔡旭东. 基于“亢害承制”理论探讨巨噬细胞极化在慢性肾脏病肾纤维化发展中的作用. 2024. doi: 10.12201/bmr.202407.00027

  思小霞, 赵青, 景江新. 超声影像组学在预测乳腺癌分子分型中的应用进展. 2024. doi: 10.12201/bmr.202410.00040

  及辉. 二甲双胍在抗衰老领域的研究进展. 2025. doi: 10.12201/bmr.202502.00005

  吴胜男, 吴佳辉, 董继宗, 蒋环宇, 王璐琦, 王欣瑶. 基于二分网络表示学习的医学实体关系预测研究. 2024. doi: 10.12201/bmr.202407.00041

• 序号	提交日期	编号	操作
  1	2025-03-14	bmr.202504.00004V1	下载

• 公开评论  匿名评论  仅发给作者 提交评论