Larcombe Alexander N, Phan Jennifer A, Kicic Anthony, Perks Kara L, Mead-Hunter Ryan, Mullins Benjamin J
Telethon Kids Institute, The University of Western Australia , Subiaco, WA , Australia .
Inhal Toxicol. 2014 Jun;26(7):409-18. doi: 10.3109/08958378.2014.909910.
Mice are commonly used in studies investigating the effects of diesel exhaust exposure on respiratory health. A plethora of studies in this field has resulted in a range of exposure protocols, from inhalation of diesel exhaust, to the administration (via various routes) of diesel exhaust particles in solution.
In this study, we compared the physiological consequences of short-term exposure to diesel exhaust via inhalation to those due to exposure to the same diesel exhaust particles suspended in solution and delivered intranasally.
Adult BALB/c mice were exposed to diesel exhaust via inhalation for 2 hours per day for 8 days. A representative, simultaneous sample of particles was collected and a second group of mice then exposed to them suspended in saline. A low and a high-dose were studied, with these matched based on respiratory parameters. Six and twenty-four hours after the last exposure we measured bronchoalveolar inflammation, lung volume, lung function and the amount of elemental carbon in alveolar macrophages.
Exposure via either route elicited pulmonary inflammation and changes in lung function. We identified significant differences in response between the two routes of exposure, with mice exposed via inhalation generally displaying more realistic dose-response relationships. Mice exposed via intranasal instillation responded more variably, with little influence of dose.
Our results suggest that selection of the route of exposure is of critical importance in studies such as this. Further, inhalation exposure, while more methodologically difficult, resulted in responses more akin to those seen in humans.
小鼠常用于研究柴油废气暴露对呼吸系统健康的影响。该领域大量的研究已产生了一系列暴露方案，从吸入柴油废气到（通过各种途径）给予溶液中的柴油废气颗粒。
在本研究中，我们比较了通过吸入短期暴露于柴油废气与通过鼻内给予悬浮于溶液中的相同柴油废气颗粒所产生的生理后果。
成年BALB/c小鼠每天通过吸入暴露于柴油废气2小时，持续8天。收集具有代表性的同步颗粒样本，然后将第二组小鼠暴露于悬浮于盐水中的这些颗粒。研究了低剂量和高剂量，根据呼吸参数进行匹配。在最后一次暴露后6小时和24小时，我们测量了支气管肺泡炎症、肺容积、肺功能以及肺泡巨噬细胞中元素碳的含量。
两种途径的暴露均引发肺部炎症和肺功能变化。我们发现两种暴露途径之间的反应存在显著差异，通过吸入暴露的小鼠通常表现出更符合实际的剂量反应关系。通过鼻内滴注暴露的小鼠反应更具变异性，剂量影响较小。
我们的结果表明，在这类研究中暴露途径的选择至关重要。此外，吸入暴露虽然在方法上更具难度，但产生的反应更类似于在人类中观察到的反应。
