Fine particulate matter (PM_2.5) is an important component of air pollution and can induce lung inflammation and oxidative stress. We hypothesized that PM_2.5 could play a role in the induction of pulmonary fibrosis. We examined whether multiple intranasal instillation of PM_2.5 can induce pulmonary fibrosis in the mouse, and also investigated the underlying pro-fibrotic signaling pathways. C57/BL6 mice were intranasally instilled with 50 μl of PM_2.5 suspension (7.8 μg/g body weight) or PBS three times a week over 3 weeks, 6 weeks or 9 weeks. To observe the recovery of pulmonary fibrosis after the termination of PM_2.5 exposure, 9 week-PM_2.5 instilled mice were also studied at 3 weeks after termination of instillation. There were significant decreases in total lung capacity (TLC) and compliance (Cchord) in the 9-week PM_2.5-instilled mice, while there were increased histological fibrosis scores with enhanced type I collagen and hydroxyproline deposition, increased mitochondrial ROS levels and NOX activity, decreased total SOD and GSH levels, accompanied by decreased mitochondrial number and aberrant mitochondrial morphology (swelling, vacuolization, cristal disruption, reduced matrix density) in PM_2.5-instilled mice. Multiple PM_2.5 instillation resulted in increased expression of TGFβ1, increases of N-Cadherin and Vimentin and a decrease of E-Cadherin. It also led to decreases in OPA1 and MFN2, and increases in Parkin, SQSTM1/p62, the ratio of light china (LC) 3B II to LC3B I, PI3k/Akt phosphorylation, and NLRP3 expression. Intranasal instillation of PM_2.5 for 9 weeks induced lung inflammation and pulmonary fibrosis, which was linked with aberrant epithelial-mesenchymal transition, oxidative stress, mitochondrial damage and mitophagy, as well as activation of TGFβ1-PI3K/Akt, TGFβ1- NOX and TGFβ1-NLRP3 pathways.

中文翻译：

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小鼠多次鼻内滴注 PM2.5 后慢性肺部炎症和肺纤维化

细颗粒物 (PM _2.5 ) 是空气污染的重要组成部分，可诱发肺部炎症和氧化应激。我们假设 PM _2.5可能在诱导肺纤维化中起作用。我们检查了多次鼻内滴注 PM _2.5是否可以诱导小鼠肺纤维化，并研究了潜在的促纤维化信号通路。C57/BL6 小鼠在 3 周、6 周或 9 周内每周 3 次鼻内滴注 50 μl PM _2.5悬浮液（7.8 μg/g 体重）或 PBS。观察终止 PM _2.5暴露后肺纤维化的恢复情况，9 周-PM _2.5在滴注终止后 3 周也对滴注小鼠进行了研究。灌注 9 周 PM _{2.5 的}小鼠的总肺活量 (TLC) 和顺应性 (Cchord) 显着降低，而组织学纤维化评分增加，I 型胶原蛋白和羟脯氨酸沉积增强，线粒体 ROS 水平和 NOX 活性增加，在 PM _2.5灌输的小鼠中，总 SOD 和 GSH 水平降低，伴随着线粒体数量的减少和异常的线粒体形态（肿胀、空泡化、晶体破裂、基质密度降低）。多个 PM _2.5滴注导致 TGFβ1 表达增加，N-钙粘蛋白和波形蛋白增加，E-钙粘蛋白减少。它还导致 OPA1 和 MFN2 减少，Parkin、SQSTM1/p62、轻瓷 (LC) 3B II 与 LC3B I 的比率、PI3k/Akt 磷酸化和 NLRP3 表达增加。鼻内滴注 PM _2.5 9 周诱导肺部炎症和肺纤维化，这与异常的上皮间质转化、氧化应激、线粒体损伤和线粒体自噬以及 TGFβ1-PI3K/Akt、TGFβ1-NOX 和 TGFβ1-的激活有关NLRP3 通路。