Abstract：
Microplastics (MPs) have been found in the air, human nasal cavity, and lung, suggesting that the respiratory tract is one of the important exposure routes for MPs. The lung is a direct target organ for injury from inhaled MPs, but data on lung injury from longer-term exposure to environmental doses of MPs are limited, and the mechanisms remain unclear. Here, C57BL/6 J mice were treated with 5 μm polystyrene (PS)-MPs by intratracheal instillation (0.6, 3, and 15 mg/kg) for 60 days to establish MPs exposure model. We found that PS-MPs lead to increased collagen fibers and decreased lung barrier permeability and lung function in lung tissue. Mechanistically, the abundance of gram-negative bacteria in the pulmonary flora increased after inhalation of PS-MPs, causing lipopolysaccharide (LPS) release. The expression of Toll-like receptor 4 (TLR4), the key receptor of LPS, was increased, and ferroptosis occurred in lung tissue cells. Further in vitro intervention experiments were performed, pulmonary flora/TLR4-induced imbalance of lung iron homeostasis is an important mechanism of PS-MPs-induced lung injury. Our study provides new evidence for lung injury caused by environmental doses of MPs and strategies to prevent it through longer-term dynamic observation.
摘要：
在空气中发现了微塑料（MPs），人类鼻腔，和肺，提示呼吸道是MP的重要暴露途径之一。肺是吸入MP损伤的直接靶器官，但是长期暴露于环境剂量的MPs的肺损伤数据有限，机制尚不清楚。这里,C57BL/6J小鼠气管内滴注5μm聚苯乙烯（PS）-MPs（0.6、3、15mg/kg）60天，建立MPs暴露模型。我们发现PS-MPs导致肺组织中胶原纤维增加，肺屏障通透性和肺功能降低。机械上,吸入PS-MPs后，肺部菌群中革兰氏阴性菌的丰度增加，导致脂多糖（LPS）的释放。Toll样受体4(TLR4)的表达,LPS的关键受体，增加了，肺组织细胞发生铁凋亡。进行了进一步的体外干预实验，肺菌群/TLR4诱导肺铁稳态失衡是PS-MPs诱导肺损伤的重要机制。我们的研究为环境剂量的MPs引起的肺损伤提供了新的证据，并通过长期动态观察来预防它。
