Lipopolysaccharide-induced endotoxemia in corn oil-preloaded mice causes an extended course of lung injury and repair and pulmonary fibrosis: A translational mouse model of acute respiratory distress syndrome.
Lipopolysaccharide-induced endotoxemia in corn oil-preloaded mice causes an extended course of lung injury and repair and pulmonary fibrosis: A translational mouse model of acute respiratory distress syndrome.
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DOI：
10.1371/journal.pone.0174327
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Zhao YY
中科院分区：
文献类型：
--
作者：
Wu C;Evans CE;Dai Z;Huang X;Zhang X;Jin H;Hu G;Song Y;Zhao YY
急性呼吸窘迫综合征（ARDS）是以急性低氧血症、呼吸衰竭、双侧肺浸润和非心源性肺水肿为特征的疾病。ARDS患者的有效治疗可能来自于这种疾病的转化小鼠模型的实验研究，其目的是描述疾病发病机制的潜在机制。然而，与人类的ARDS过程相反，ARDS的小鼠模型可能受到其从受伤到恢复状态的快速进展的限制。此外，目前的ARDS小鼠模型不能概括人类ARDS发病机制的某些突出方面。在这项研究中，我们开发了一种改进的内毒素血症小鼠ARDS模型，该模型与临床ARDS的许多特征相似，包括在向预载玉米油的小鼠腹腔注射脂多糖（LPS）后损伤和恢复的延长过程以及纤维化的发展。与单独接受LPS的小鼠相比，接受玉米油和LPS的小鼠表现出肺损伤和修复的延长过程，发生在>2周而不是3- 5天的时间内。重要的是，LPS攻击玉米油预载小鼠导致肺纤维化在修复阶段，经常看到在ARDS患者。总之，这种简单的新型小鼠ARDS模型可以代表一种有价值的实验工具，以阐明调节ARDS患者肺损伤和修复的机制。
Acute respiratory distress syndrome (ARDS) is characterized by acute hypoxemia respiratory failure, bilateral pulmonary infiltrates, and pulmonary edema of non-cardiac origin. Effective treatments for ARDS patients may arise from experimental studies with translational mouse models of this disease that aim to delineate the mechanisms underlying the disease pathogenesis. Mouse models of ARDS, however, can be limited by their rapid progression from injured to recovery state, which is in contrast to the course of ARDS in humans. Furthermore, current mouse models of ARDS do not recapitulate certain prominent aspects of the pathogenesis of ARDS in humans. In this study, we developed an improved endotoxemic mouse model of ARDS resembling many features of clinical ARDS including extended courses of injury and recovery as well as development of fibrosis following i.p. injection of lipopolysaccharide (LPS) to corn oil-preloaded mice. Compared with mice receiving LPS alone, those receiving corn oil and LPS exhibited extended course of lung injury and repair that occurred over a period of >2 weeks instead of 3–5days. Importantly, LPS challenge of corn oil-preloaded mice resulted in pulmonary fibrosis during the repair phase as often seen in ARDS patients. In summary, this simple novel mouse model of ARDS could represent a valuable experimental tool to elucidate mechanisms that regulate lung injury and repair in ARDS patients.