Acute pulmonary dose-responses to inhaled multi-walled carbon nanotubes
Acute pulmonary dose-responses to inhaled multi-walled carbon nanotubes
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DOI：
10.3109/17435390.2012.719649
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发表时间：
2013-11-01
期刊：
影响因子：
5
通讯作者：
Castranova, Vincent
中科院分区：
文献类型：
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作者：
Porter, Dale W.;Hubbs, Ann F.;Castranova, Vincent
本研究探讨了吸入多壁碳纳米管（MWCNT）的体内肺毒性。小鼠吸入雾化多壁碳纳米管（10毫克/米（3），5小时/天）2，4，8或12天。多壁碳纳米管肺负荷与暴露持续时间呈线性相关。通过测定全肺灌洗（WLL）多形核白细胞（PMN）来评估MWCNT诱导的肺部炎症。以WLL液LDH活性评价肺细胞毒性。测定WLL液体白蛋白浓度作为肺泡气-血屏障完整性的标志。与对照组相比，这些参数在MWCNT暴露小鼠中显著增加，并且具有剂量依赖性。在肺中发现的组织学改变包括（1）支气管中心性炎症，（2）细支气管上皮增生和肥大，（3）纤维化，（4）血管变化和（5）罕见的胸膜穿透。多壁碳纳米管移位到淋巴结中，在8或12天后深副皮质扩张。急性吸入多壁碳纳米管可引起剂量依赖性的肺部炎症和损伤，并迅速发展为肺纤维化，也表明多壁碳纳米管吸入暴露后可到达胸膜。
This study investigated the in vivo pulmonary toxicity of inhaled multi-walled carbon nanotubes (MWCNT). Mice-inhaled aerosolized MWCNT (10 mg/m(3), 5 h/day) for 2, 4, 8 or 12 days. MWCNT lung burden was linearly related to exposure duration. MWCNT-induced pulmonary inflammation was assessed by determining whole lung lavage (WLL) polymorphonuclear leukocytes (PMN). Lung cytotoxicity was assessed by WLL fluid LDH activities. WLL fluid albumin concentrations were determined as a marker of alveolar air-blood barrier integrity. These parameters significantly increased in MWCNT-exposed mice versus controls and were dose-dependent. Histopathologic alterations identified in the lung included (1) bronciolocentric inflammation, (2) bronchiolar epithelial hyperplasia and hypertrophy, (3) fibrosis, (4) vascular changes and (5) rare pleural penetration. MWCNT translocated to the lymph node where the deep paracortex was expanded after 8 or 12 days. Acute inhalation of MWCNT induced dose-dependent pulmonary inflammation and damage with rapid development of pulmonary fibrosis, and also demonstrated that MWCNT can reach the pleura after inhalation exposure.