Abstract：
Polystyrene microplastics (PS-MP) and dibutyl phthalate (DBP) are plastic pollution derivatives (PPDs) commonly found in the natural environment. To investigate the effects of PPD exposure on the risk of allergic asthma, we established a PPD exposure group in a mouse model. The dose administered for PS-MP was 0.1 mg/d and for DBP was 30 mg/kg/d, with a 5-week oral administration period. The pathological changes of airway tissue and the increase of oxidative stress and inflammatory response confirmed that PPD aggravated eosinophilic allergic asthma in mice. The mitochondrial morphological changes and metabolomics of mice confirmed that ferrotosis and oxidative stress played key roles in this process. Treatment with 100 mg/Kg deferoxamine (DFO) provided significant relief, and metabolomic analysis of lung tissue supported the molecular toxicological. Our findings suggest that the increased levels of reactive oxygen species (ROS) in the lungs lead to Th2-mediated eosinophilic inflammation, characterized by elevated IL-4, IL-5, and eosinophils, and reduced INF-γ levels. This inflammatory response is mediated by the NFκB pathway and exacerbates type I hypersensitivity through increased IL-4 production. In this study, the molecular mechanism by which PPD aggravates asthma in mice was elucidated, which helps to improve the understanding of the health effects of PPD and lays a theoretical foundation for addressing the health risks posed by PPD.
摘要：
聚苯乙烯微塑料（PS-MP）和邻苯二甲酸二丁酯（DBP）是自然环境中常见的塑料污染衍生物（PPD）。探讨PPD暴露对过敏性哮喘发病风险的影响,我们在小鼠模型中建立了PPD暴露组。PS-MP给药剂量为0.1mg/d，DBP给药剂量为30mg/kg/d，5周口服给药。气道组织病理变化和氧化应激和炎症反应的增加证实PPD加重了小鼠嗜酸性粒细胞过敏性哮喘。小鼠线粒体形态变化和代谢组学研究证实，铁性凋亡和氧化应激在这一过程中发挥了关键作用。用100毫克/公斤去铁胺（DFO）治疗可明显缓解，和肺组织的代谢组学分析支持分子毒理学。我们的研究结果表明，肺部活性氧（ROS）水平的增加导致Th2介导的嗜酸性粒细胞炎症，以IL-4、IL-5和嗜酸性粒细胞升高为特征，并降低INF-γ水平。这种炎症反应由NFκB途径介导，并通过增加IL-4的产生加剧了I型超敏反应。在这项研究中,阐明了PPD加重小鼠哮喘的分子机制，有助于提高对PPD健康效应的认识,为解决PPD带来的健康风险奠定理论基础。
