Department of Toxicology and Sanitary Chemistry, Capital Medical University, Beijing, 100069, PR China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, PR China.
Department of Toxicology and Sanitary Chemistry, Capital Medical University, Beijing, 100069, PR China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing, 100069, PR China.
J Hazard Mater. 2020 Mar 5;385:121566. doi: 10.1016/j.jhazmat.2019.121566. Epub 2019 Nov 4.
Up to now, while some toxicological studies have identified pulmonary fibrosis immediately induced by long-term PM exposure, there has been no evidence indicating, whether short-term exposure can lead to post-exposure development of pulmonary fibrosis. Here, we treated rats with PM for 1 month (10 times), followed by normal feeding for 18 months. F-FDG intake, which is linked with the initiation and development of pulmonary fibrosis in living bodies, was found to gradually increase in lung following exposure through micro PET/CT imaging. Histolopathological examination revealed continuous deterioration of pulmonary injury post-exposure. Collagen deposition and hydroxyproline content continued to increase all along in the post-exposure duration, indicating pulmonary fibrosis development. Chronic and persistent induction of pulmonary inflammatory gene expression (Tnf, Il1b, Il6, Ccl2, and Icam1), epithelial mesenchymal transition (EMT, reduction of E-cadherin and elevation of fibronectin) and RelA/p65 upregulation, as well as serum inflammatory cytokine production, were also found in PM-treated rats. Pulmonary oxidative stress, manifested by increase of MDA and decrease of GSH and SOD, was induced during exposure but disappeared in later post-exposure duration. These results suggested that short-term PM exposure could lead to sustained post-exposure pulmonary fibrosis development, which was mediated by oxidative-stress-initiated NF-κB/inflammation/EMT pathway.
到目前为止，虽然一些毒理学研究已经确定了长期 PM 暴露会立即引起肺纤维化，但没有证据表明短期暴露是否会导致暴露后肺纤维化的发展。在这里，我们用 PM 处理大鼠 1 个月（10 次），然后正常喂养 18 个月。通过 micro PET/CT 成像发现，与体内肺纤维化的发生和发展相关的 F-FDG 摄入在暴露后逐渐增加。组织病理学检查显示暴露后肺损伤持续恶化。胶原沉积和羟脯氨酸含量在整个暴露过程中持续增加，表明肺纤维化的发展。慢性和持续诱导的肺炎症基因表达（Tnf、Il1b、Il6、Ccl2 和 Icam1）、上皮间质转化（EMT，E-钙粘蛋白减少和纤维连接蛋白升高）和 RelA/p65 上调，以及血清炎症细胞因子的产生，也在 PM 处理的大鼠中发现。暴露期间诱导了肺氧化应激，表现为 MDA 增加和 GSH 和 SOD 减少，但在后期暴露期间消失。这些结果表明，短期 PM 暴露可导致持续的暴露后肺纤维化发展，这是由氧化应激引发的 NF-κB/炎症/EMT 途径介导的。
