Lange Matthias, Cox Robert A, Traber Daniel L, Hamahata Atsumori, Nakano Yoshimitsu, Traber Lillian D, Enkhbaatar Perenlei
Department of Anesthesiology, Investigational Intensive Care Unit, University of Texas Medical Branch and Shriners Burns Hospital for Children, Galveston, Texas 77555, USA.
Exp Lung Res. 2013 May-Jun;39(4-5):201-6. doi: 10.3109/01902148.2013.794254. Epub 2013 May 7.
Large animal models are valuable tools in biological and medical lung research. Despite the existence of established large animal models, the scientific progress requires more detailed description and expansion of established methods. Previously, we established an ovine model of acute lung injury and subsequent bacterial instillation into the lungs. The current study was designed to assess the time course of early lung histopathological alterations in a large animal model. Injury was induced by smoke inhalation and instillation of live Pseudomonas aeruginosa into the lungs. After 4, 8, 12, 18, and 24 hours, respectively, lung tissue was harvested and histopathological changes were evaluated (n = 4 each). Additional four sheep received no injury and only lung tissue was taken. In injured animals, bronchial obstruction score increased over time and was significantly elevated from 12 to 24 hours (P < .05 versus no injury). Inflammation score was significantly increased at 12 and 18 hours (P < .05 versus no injury). Hemorrhage score was increased at 8 and 12 hours (P < .05 versus no injury). Alveolar edema score was significantly higher in injured sheep at 8, 18, and 24 hours (P < .05 each versus no injury). In conclusion, bronchial obstruction and alveolar edema scores significantly increased over time and reached a plateau, while both inflammation and hemorrhage scores were transiently increased peaking around the 12-hour time point. This information improves the understanding of lung histopathological alterations following acute lung injury and pulmonary infection and may help optimizing the timing of study interventions and evaluation time points in future experiments with this model.
大型动物模型是生物和医学肺部研究中的重要工具。尽管已经有了成熟的大型动物模型，但科学的进步需要对现有方法进行更详细的描述和扩展。此前，我们建立了急性肺损伤并随后向肺内注入细菌的绵羊模型。本研究旨在评估大型动物模型中早期肺组织病理学改变的时间进程。通过吸入烟雾和向肺内注入活的铜绿假单胞菌诱导损伤。分别在4、8、12、18和24小时后，采集肺组织并评估组织病理学变化（每组n = 4）。另外四只绵羊未受伤，仅采集肺组织。在受伤动物中，支气管阻塞评分随时间增加，在12至24小时显著升高（与未受伤相比，P < .05）。炎症评分在12和18小时显著增加（与未受伤相比，P < .05）。出血评分在8和12小时增加（与未受伤相比，P < .05）。肺泡水肿评分在受伤绵羊的8、18和24小时显著更高（与未受伤相比，每组P < .05）。总之，支气管阻塞和肺泡水肿评分随时间显著增加并达到平台期，而炎症和出血评分均短暂增加，在12小时左右达到峰值。这些信息有助于加深对急性肺损伤和肺部感染后肺组织病理学改变的理解，并可能有助于在该模型的未来实验中优化研究干预的时机和评估时间点。
