Development of animal models for the acute respiratory distress syndrome
Development of animal models for the acute respiratory distress syndrome
复制标题
DOI：
10.1242/dmm.001677
复制
发表时间：
2009-05-01
影响因子：
4.3
通讯作者：
Blackwell, Timothy S.
中科院分区：
文献类型：
--
作者：
Bastarache, Julie A.;Blackwell, Timothy S.
肺实质的损伤导致急性呼吸窘迫综合征（ARDS），其是在各种损伤（包括败血症、多发性创伤、肺炎、吸入胃内容物和严重烧伤）后发展的呼吸衰竭和死亡的常见且危及生命的原因。ARDS的发病机制是复杂的，包括肺泡-毛细血管屏障的丧失和富含蛋白质的液体充斥空气空间;肺泡上皮细胞损伤;中性粒细胞和巨噬细胞的流入;以及由于凝血激活和纤维蛋白溶解抑制而导致的纤维蛋白沉积。这些变化在初始事件发生后数小时至数天内发生，通常需要数天或数周才能解决。尽管经过数十年的研究，只有一种疗法（低潮气量通气）已被证明可以降低ARDS的死亡率。进一步研究这种毁灭性疾病的发病机制对于开发针对特定疾病机制的新型和特定疗法至关重要。不幸的是，没有一种单一的ARDS动物模型能复制患者中所见的复杂病理生理学变化。这是ARDS研究中的一个严重限制，并阻碍了该领域的科学和治疗进展。在这里，我们讨论了这种综合征的主要特点，强调目前的动物模型的局限性，并提出了新的方法来研究发病机制的关键组成部分。希望随着新技术和方法的出现，ARDS科学进步的障碍将被克服。
Injury to the lung parenchyma results in the acute respiratory distress syndrome (ARDS), which is a common and life-threatening cause of respiratory failure and mortality that develops after a variety of insults, including sepsis, multiple trauma, pneumonia, aspiration of gastric contents and severe burns. The pathogenesis of ARDS is complex with loss of the alveolar-capillary barrier and flooding of the airspaces with protein-rich fluid; injury to the alveolar epithelium; an influx of neutrophils and macrophages; and fibrin deposition as a result of activation of coagulation and inhibition of fibrinolysis. These changes develop over hours to a few days after the initiating event and often take days or weeks to resolve. Despite decades of research, there is only one therapy (low tidal volume ventilation) that has been shown to reduce mortality in ARDS. Further research into the pathogenesis of this devastating condition is crucial for the development of novel and specific therapies that target specific disease mechanisms. Unfortunately, no single animal model of ARDS replicates the complex pathophysiological changes seen in patients. This is a severe limitation in the study of ARDS and has impaired scientific and therapeutic progress in this field. Here, we discuss the primary features of this syndrome, highlight limitations of current animal models and suggest new approaches to investigate key components of pathogenesis. Hopefully, as new technologies and approaches emerge, barriers to scientific progress in ARDS will be overcome.