Yang Lin, Xu Fei, Zhao Shuaiqi, Zeng Yuling, Wu Qiong, Zhang Ling, Shi Saige, Zhang Fengquan, Li Juan, An Zhen, Li Huijun, Wu Hui, Song Jie, Wu Weidong
School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province 453003, China.
School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province 453003, China.
Ecotoxicol Environ Saf. 2025 Jan 15;290:117626. doi: 10.1016/j.ecoenv.2024.117626. Epub 2024 Dec 30.
Co-exposure to ground-level ozone (O) and fine particles (PM, ≤ 2.5 µm in diameter) has become a primary scenario for air pollution exposure of urbanites in China. Recent studies have suggested a synergistic effect of PM and O on induction of lung inflammatory injury. However, the underlying mechanisms for respiratory toxicity induced by this co-exposure have not been adequately elucidated. In this study, a realistic exposure was based to set up the co-exposure condition of an animal model. Specifically, eighty male C57BL/6 mice (10 months old) were randomly divided into four groups: control, O, PM and co-exposure (O + PM). Mice in the co-exposure group breathed O and orally inhaled PM suspension. The scenario for O exposure was 0.6 ppm, 4 h/d, for 30 consecutive days while that for PM exposure was oral inhalation of PM suspension (5.6 mg/kg bw) once every other day and 4 h prior to O exposure. After last exposure, bronchoalveolar lavage fluids (BALF) were collected for inflammatory biomarker measurement, 16S rRNA sequencing and metabolite profiling. Lung tissues were processed for histological examination. The results demonstrated that co-exposure to O and PM exacerbated the pathological changes and inflammatory response induced by O or PM. Further studies revealed that co-exposure to O and PM increased the abundance of Prevotella in the airways and caused more severe metabolic disorders compared to O or PM exposure. Spearman correlation analysis demonstrated correlations among airway microbiota dysbiosis, metabolic disorder, inflammation, and pathological alterations induced by co-exposure to O and PM. In summary, co-exposure to O and PM worsens airway inflammatory injury, possibly through interrelated airway microbiota dysbiosis and metabolic disorder.
同时暴露于地面臭氧（O）和细颗粒物（PM，直径≤2.5微米）已成为中国城市居民空气污染暴露的主要情况。最近的研究表明，PM和O对诱导肺部炎症损伤具有协同作用。然而，这种共同暴露诱导的呼吸毒性的潜在机制尚未得到充分阐明。在本研究中，基于实际暴露情况建立了动物模型的共同暴露条件。具体而言，80只雄性C57BL/6小鼠（10个月大）被随机分为四组：对照组、O组、PM组和共同暴露组（O+PM）。共同暴露组的小鼠吸入O并经口吸入PM悬浮液。O暴露的情况为0.6 ppm，每天4小时，连续30天；而PM暴露的情况为每隔一天经口吸入PM悬浮液（5.6 mg/kg体重），并在O暴露前4小时进行。末次暴露后，收集支气管肺泡灌洗液（BALF）用于炎症生物标志物测量、16S rRNA测序和代谢物谱分析。对肺组织进行组织学检查。结果表明，同时暴露于O和PM会加剧由O或PM诱导的病理变化和炎症反应。进一步的研究表明，与O或PM暴露相比，同时暴露于O和PM会增加气道中普雷沃氏菌的丰度，并导致更严重的代谢紊乱。Spearman相关性分析表明，同时暴露于O和PM所诱导的气道微生物群失调、代谢紊乱、炎症和病理改变之间存在相关性。总之，同时暴露于O和PM会加重气道炎症损伤，可能是通过相关的气道微生物群失调和代谢紊乱实现的。
