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气管内滴注大鼠后,个体分散的多壁碳纳米管在肺部的生物学反应和形态评估。

Biological response and morphological assessment of individually dispersed multi-wall carbon nanotubes in the lung after intratracheal instillation in rats.

机构信息

Research Institute of Science for Safety and Sustainability, National Institute of Advanced Industrial Science and Technology, 16-1 Onagawa, Tsukuba, Ibaraki 305-8569, Japan.

出版信息

Toxicology. 2010 Oct 29;276(3):143-53. doi: 10.1016/j.tox.2010.07.021. Epub 2010 Aug 7.

Abstract

Biological responses of multi-wall carbon nanotubes (MWCNTs) were assessed after a single intratracheal instillation in rats. The diameter and median length of the MWCNTs used in this study were approximately 60 nm and 1.5 μm, respectively. Groups of male Sprague-Dawley rats were intratracheally instilled with 0.04, 0.2, or 1 mg/kg of the individually dispersed MWCNT suspension. After instillation, the bronchoalveolar lavage fluid was assessed for inflammatory cells and markers, and the lung, liver, kidney, spleen, and cerebrum were histopathologically evaluated at 3-day, 1-week, 1-month, 3-month, and 6-month post-exposure. Transient pulmonary inflammatory responses were observed only in the lungs of the group of rats exposed to 1 mg/kg of MWCNTs. Morphology of the instilled MWCNTs in the lungs of rats was assessed using light microscopy and transmission electron microscopy (TEM). Light microscopy examination revealed that MWCNTs deposited in the lungs of the rats were typically phagocytosed by the alveolar macrophages and these macrophages were consequently accumulated in the alveoli until 6-month post-exposure. The 400 TEM images obtained showed that all MWCNTs were located in the alveolar macrophages or macrophages in the interstitial tissues, and MWCNTs were not located in the cells of the interstitial tissues. There was no evidence of chronic inflammation, such as angiogenesis or fibrosis, induced by MWCNT instillation. These results suggest that MWCNTs were being processed and cleared by alveolar macrophages.

摘要

多壁碳纳米管(MWCNTs)的生物反应在大鼠单次气管内滴注后进行了评估。本研究中使用的 MWCNTs 的直径和中值长度约为 60nm 和 1.5μm。雄性 Sprague-Dawley 大鼠组通过气管内滴注 0.04、0.2 或 1mg/kg 的单独分散的 MWCNT 悬浮液。滴注后,评估支气管肺泡灌洗液中的炎症细胞和标志物,并在暴露后 3 天、1 周、1 个月、3 个月和 6 个月时对肺、肝、肾、脾和大脑进行组织病理学评估。仅在暴露于 1mg/kg MWCNTs 的大鼠组的肺部观察到短暂的肺部炎症反应。使用光学显微镜和透射电子显微镜(TEM)评估在大鼠肺部滴注的 MWCNTs 的形态。光学显微镜检查显示,MWCNTs 沉积在大鼠肺部中,通常被肺泡巨噬细胞吞噬,这些巨噬细胞随后在肺泡中积聚,直到暴露后 6 个月。获得的 400 个 TEM 图像显示,所有 MWCNTs 都位于肺泡巨噬细胞或间质组织中的巨噬细胞中,MWCNTs 不在间质组织的细胞中。没有证据表明 MWCNT 滴注引起慢性炎症,如血管生成或纤维化。这些结果表明,MWCNTs 被肺泡巨噬细胞处理和清除。

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