Short-term PM2.5 exposure induces sustained pulmonary fibrosis development during post-exposure period in rats
Short-term PM2.5 exposure induces sustained pulmonary fibrosis development during post-exposure period in rats
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短期 PM2.5 暴露可诱导大鼠暴露后持续肺纤维化发展
DOI：
10.1016/j.jhazmat.2019.121566
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发表时间：
2020-03-05
影响因子：
13.6
通讯作者：
Sun, Zhiwei
中科院分区：
文献类型：
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作者：
Sun, Baiyang;Shi, Yanfeng;Sun, Zhiwei
到目前为止，虽然一些毒理学研究已经确定了长期PM2.5暴露会立即诱导肺纤维化，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（2.5）治疗大鼠1个月（10次），然后正常喂养18个月。通过微型PET/CT成像发现，与活体中肺纤维化的开始和发展相关的F-18-FDG摄入在暴露后在肺中逐渐增加。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暴露后沿着持续增加，表明肺纤维化的发展。慢性和持续诱导肺炎症基因表达（TNF，IL 1b，IL 6，CCl 2和ICAM 1），上皮间质转化（EMT，减少E-钙粘蛋白和纤维连接蛋白的升高）和RelA/p65上调，以及血清炎症细胞因子的产生，也被发现在PM2.5治疗的大鼠。暴露过程中可引起肺组织氧化应激反应，表现为MDA含量增加，GSH和SOD含量降低，但在暴露后较长时间内氧化应激反应消失。这些结果表明，短期PM2. 5暴露可导致暴露后肺纤维化的持续发展，这是由氧化应激启动的NF-κ B B/炎症/EMT通路介导的。
Up to now, while some toxicological studies have identified pulmonary fibrosis immediately induced by long-term PM2.5 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(2.5 )for 1 month (10 times), followed by normal feeding for 18 months. F-18-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 PM2.5-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 PM2.5 exposure could lead to sustained post-exposure pulmonary fibrosis development, which was mediated by oxidative-stress-initiated NF-kappa B/inflammation/EMT pathway.