Alluri Ravi, Kutscher Hilliard L, Mullan Barbara A, Davidson Bruce A, Knight Paul R
Department of Anesthesiology, University at Buffalo, State University of New York; Department of Anesthsiology, Veterans Admistration Western New York Healthcare System.
Institute of Lasers, Photonics and Biophotonics, University at Buffalo, State University of New York.
J Vis Exp. 2017 Feb 26(120):54700. doi: 10.3791/54700.
Acid pneumonitis is a major cause of sterile acute lung injury (ALI) in humans. Acid pneumonitis spans the clinical spectrum from asymptomatic to acute respiratory distress syndrome (ARDS), characterized by neutrophilic alveolitis, and injury to both alveolar epithelium and vascular endothelium. Clinically, ARDS is defined by acute onset of hypoxemia, bilateral patchy pulmonary infiltrates and non-cardiogenic pulmonary edema. Human studies have provided us with valuable information about the physiological and inflammatory changes in the lung caused by ARDS, which has led to various hypotheses about the underling mechanisms. Unfortunately, difficulties determining the etiology of ARDS, as well as a wide range of pathophysiology have resulted in a lack of critical information that could be useful in developing therapeutic strategies. Translational animal models are valuable when their pathogenesis and pathophysiology accurately reproduce a concept proven in both in vitro and clinical settings. Although large animal models (e.g., sheep) share characteristics of the anatomy of human trachea-bronchial tree, murine models provide a host of other advantages including: low cost; short reproductive cycle lending itself to greater data acquisition; a well understood immunologic system; and a well characterized genome leading to the availability of a variety of gene deletion and transgenic strains. A robust model of low pH induced ARDS requires a murine ALI that targets mainly the alveolar epithelium, secondarily the vascular endothelium, as well as the small airways leading to the alveoli. Furthermore, a reproducible injury with wide differences between different injurious and non-injurious insults is important. The murine gastric acid aspiration model presented here using hydrochloric acid employs an open tracheostomy and recreates a pathogenic scenario that reproduces the low pH pneumonitis injury in humans. Additionally, this model can be used to examine interaction of a low pH insult with other pulmonary injurious entities (e.g., food particles, pathogenic bacteria).
酸性肺炎是人类无菌性急性肺损伤（ALI）的主要原因。酸性肺炎涵盖了从无症状到急性呼吸窘迫综合征（ARDS）的临床范围，其特征为嗜中性肺泡炎以及肺泡上皮和血管内皮损伤。临床上，ARDS的定义是急性低氧血症、双侧斑片状肺部浸润和非心源性肺水肿。人体研究为我们提供了有关ARDS引起的肺部生理和炎症变化的宝贵信息，这导致了关于潜在机制的各种假设。不幸的是，确定ARDS病因的困难以及广泛的病理生理学导致缺乏对制定治疗策略可能有用的关键信息。当翻译动物模型的发病机制和病理生理学准确再现体外和临床环境中已证实的概念时，它们就很有价值。尽管大型动物模型（如绵羊）具有人类气管支气管树的解剖学特征，但小鼠模型具有许多其他优点，包括：成本低；繁殖周期短，便于获取更多数据；免疫系统已为人熟知；基因组特征明确，可获得多种基因缺失和转基因品系。一个强大的低pH诱导ARDS模型需要一个主要针对肺泡上皮、其次针对血管内皮以及通向肺泡的小气道的小鼠ALI。此外，不同损伤和非损伤性刺激之间存在显著差异的可重复性损伤很重要。本文介绍的使用盐酸的小鼠胃酸吸入模型采用开放式气管切开术，重现了一种致病情况，可再现人类低pH肺炎损伤。此外，该模型可用于研究低pH刺激与其他肺部损伤因素（如食物颗粒、病原菌）的相互作用。
