Master Program in Clinical Pharmacogenomics and Pharmacoproteomics, College of Pharmacy, Taipei Medical University, Mailing address: 250 Wuxing St, Taipei, 11031, Taiwan.
International Ph.D. Program in Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Part Fibre Toxicol. 2021 Jun 25;18(1):24. doi: 10.1186/s12989-021-00417-y.
Exposure to air pollution exerts direct effects on respiratory organs; however, molecular alterations underlying air pollution-induced pulmonary injury remain unclear. In this study, we investigated the effect of air pollution on the lung tissues of Sprague-Dawley rats with whole-body exposure to traffic-related PM (particulate matter < 1 μm in aerodynamic diameter) pollutants and compared it with that in rats exposed to high-efficiency particulate air-filtered gaseous pollutants and clean air controls for 3 and 6 months. Lung function and histological examinations were performed along with quantitative proteomics analysis and functional validation.
Rats in the 6-month PM-exposed group exhibited a significant decline in lung function, as determined by decreased FEF and FEV/FVC; however, histological analysis revealed earlier lung damage, as evidenced by increased congestion and macrophage infiltration in 3-month PM-exposed rat lungs. The lung tissue proteomics analysis identified 2673 proteins that highlighted the differential dysregulation of proteins involved in oxidative stress, cellular metabolism, calcium signalling, inflammatory responses, and actin dynamics under exposures to PM and gaseous pollutants. The presence of PM specifically enhanced oxidative stress and inflammatory reactions under subchronic exposure to traffic-related PM and suppressed glucose metabolism and actin cytoskeleton signalling. These factors might lead to repair failure and thus to lung function decline after chronic exposure to traffic-related PM. A detailed pathogenic mechanism was proposed to depict temporal and dynamic molecular regulations associated with PM- and gaseous pollutants-induced lung injury.
This study explored several potential molecular features associated with early lung damage in response to traffic-related air pollution, which might be used to screen individuals more susceptible to air pollution.
暴露于空气污染会对呼吸器官产生直接影响；然而，空气污染引起的肺损伤的潜在分子改变仍不清楚。在这项研究中，我们研究了全身暴露于交通相关 PM（空气动力学直径<1μm 的颗粒物）污染物对 Sprague-Dawley 大鼠肺组织的影响，并将其与暴露于高效空气颗粒物过滤气态污染物和清洁空气对照的大鼠进行了比较，暴露时间为 3 个月和 6 个月。进行了肺功能和组织学检查，同时进行了定量蛋白质组学分析和功能验证。
6 个月 PM 暴露组大鼠的肺功能明显下降，表现为 FEF 和 FEV/FVC 降低；然而，组织学分析显示 3 个月 PM 暴露大鼠的肺更早出现损伤，表现为充血和巨噬细胞浸润增加。肺组织蛋白质组学分析鉴定出 2673 种蛋白质，这些蛋白质突出了参与氧化应激、细胞代谢、钙信号、炎症反应和肌动蛋白动力学的蛋白质在 PM 和气态污染物暴露下的差异失调。PM 的存在特别增强了交通相关 PM 亚慢性暴露下的氧化应激和炎症反应，并抑制了葡萄糖代谢和肌动蛋白细胞骨架信号。这些因素可能导致修复失败，从而导致长期暴露于交通相关 PM 后肺功能下降。提出了一个详细的发病机制，以描述与 PM 和气态污染物引起的肺损伤相关的时间和动态分子调节。
本研究探讨了一些与交通相关空气污染引起的早期肺损伤相关的潜在分子特征，这些特征可能用于筛选更易受空气污染影响的个体。
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