Lung response to multi-walled carbon nanotube exposure in rats.

The projected increase in the production and use of nanomaterials is expected to result in a corresponding increase in human exposure, potentially resulting in significant morbidity and mortality. Currently, the lung toxicity of multi-walled carbon nanotubes (MWCNT), a prototype nanomaterial, was investigated in a rat model. The rats were exposed by whole-body inhalation to air (controls) or MWCNT (6 hours/day, 3 days) to result in cumulative doses of 180, 90, 45, 22.5, or 11.25 mg/m3. Lung toxicity and gene expression profiles were determined in the lungs of the control and MWCNT exposed rats one day following termination of the exposures. Moderate lung histological changes, indicative of toxicity, were detected in rats exposed to MWCNT at doses > 45 mg/m3. Changes in toxicity parameters including, lactate dehydrogenase (LDH) activity, oxidant production, cell counts of phagocytes, and cytokine levels were detected in the bronchoalveolar lavage of rats exposed to > 22.5 mg/m3 MWCNT, compared with the air controls. Lung gene expression profiling detected differences in transcript levels (fold change >1.5 and FDR p<0.05) of several genes in the rats exposed to >22.5 mg/m3 MWCNT, compared with the controls. The changes in lung toxicity and gene expression profiles exhibited a dose-response to the MWCNT administered in the rats.随着纳米材料生产与应用规模的预计增长，人类的纳米材料暴露水平也将相应提升，这可能会引发严重的发病与死亡事件。本研究以大鼠为模型，针对作为原型纳米材料的多壁碳纳米管（multi-walled carbon nanotubes, MWCNT）的肺毒性开展了相关探究。实验大鼠通过全身吸入方式分别暴露于空气（对照组）或MWCNT环境中，暴露方案为每日6小时、连续3天，累积暴露剂量分别设置为180、90、45、22.5及11.25 mg/m³。在暴露结束1天后，我们对对照组与MWCNT暴露组大鼠的肺部组织分别开展了肺毒性指标与基因表达谱检测。在暴露剂量高于45 mg/m³的MWCNT暴露大鼠中，可观察到提示肺毒性的中度肺部组织病理学改变。与空气对照组相比，暴露于剂量高于22.5 mg/m³ MWCNT的大鼠支气管肺泡灌洗液中，可检测到多项毒性参数的变化，包括乳酸脱氢酶（lactate dehydrogenase, LDH）活性、活性氧生成量、吞噬细胞计数以及细胞因子水平。肺部基因表达谱分析显示，相较于对照组，暴露于剂量高于22.5 mg/m³ MWCNT的大鼠体内多个基因的转录水平出现显著差异（倍数变化>1.5且错误发现率（FDR）校正P值<0.05）。大鼠肺部的毒性变化与基因表达谱改变均呈现出与MWCNT暴露剂量相关的剂量-反应关系。