Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China; Department of Respiratory and Critical Care Medicine, Ganzhou people's Hospital, Ganzhou, China.
Ecotoxicol Environ Saf. 2024 Jun 1;277:116357. doi: 10.1016/j.ecoenv.2024.116357. Epub 2024 Apr 26.
Polystyrene microplastics (PS-MPs) are new types of environmental pollutant that have garnered significant attention in recent years since they were found to cause damage to the human respiratory system when they are inhaled. The pulmonary fibrosis is one of the serious consequences of PS-MPs inhalation. However, the impact and underlying mechanisms of PS-MPs on pulmonary fibrosis are not clear. In this study, we studied the potential lung toxicity and PS-MPs-developed pulmonary fibrosis by long-term intranasal inhalation of PS-MPs. The results showed that after exposing to the PS-MPs, the lungs of model mouse had different levels of damage and fibrosis. Meanwhile, exposing to the PS-MPs resulted in a markedly decrease in glutathione (GSH), an increase in malondialdehyde (MDA), and iron overload in the lung tissue of mice and alveolar epithelial cells (AECs). These findings suggested the occurrence of PS-MP-induced ferroptosis. Inhibitor of ferroptosis (Fer-1) had alleviated the PS-MPs-induced ferroptosis. Mechanically, PS-MPs triggered cell ferroptosis and promoted the development of pulmonary fibrosis via activating the cGAS/STING signaling pathway. Inhibition of cGAS/STING with G150/H151 attenuated pulmonary fibrosis after PS-MPs exposure. Together, these data provided novel mechanistic insights of PS-MPs-induced pulmonary fibrosis and a potential therapeutic paradigm.
聚苯乙烯微塑料（PS-MPs）是近年来新出现的一类环境污染物，由于其被发现吸入后会对人体呼吸系统造成损害而引起了广泛关注。肺纤维化是 PS-MPs 吸入的严重后果之一。然而，PS-MPs 对肺纤维化的影响及其潜在机制尚不清楚。在这项研究中，我们通过长期鼻腔内吸入 PS-MPs 来研究 PS-MPs 对肺部的潜在毒性和 PS-MPs 诱导的肺纤维化。结果表明，暴露于 PS-MPs 后，模型小鼠的肺部出现不同程度的损伤和纤维化。同时，暴露于 PS-MPs 导致小鼠肺组织和肺泡上皮细胞（AECs）中谷胱甘肽（GSH）明显减少，丙二醛（MDA）增加，铁超载。这些发现表明发生了 PS-MP 诱导的铁死亡。铁死亡抑制剂（Fer-1）缓解了 PS-MPs 诱导的铁死亡。机制上，PS-MPs 通过激活 cGAS/STING 信号通路引发细胞铁死亡，促进肺纤维化的发展。用 G150/H151 抑制 cGAS/STING 可减轻 PS-MPs 暴露后的肺纤维化。总之，这些数据为 PS-MPs 诱导的肺纤维化提供了新的机制见解和潜在的治疗范例。
