Bastarache Julie A, Blackwell Timothy S
Department of Medicine, Division of Allergy, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Dis Model Mech. 2009 May-Jun;2(5-6):218-23. doi: 10.1242/dmm.001677.
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.
肺实质损伤会导致急性呼吸窘迫综合征（ARDS），这是呼吸衰竭和死亡的常见且危及生命的原因，在包括脓毒症、多发性创伤、肺炎、胃内容物误吸和严重烧伤等多种损伤后发生。ARDS的发病机制复杂，包括肺泡-毛细血管屏障丧失、富含蛋白质的液体充斥气腔；肺泡上皮损伤；中性粒细胞和巨噬细胞流入；以及由于凝血激活和纤维蛋白溶解抑制导致的纤维蛋白沉积。这些变化在起始事件后的数小时至数天内发展，通常需要数天或数周才能解决。尽管经过数十年的研究，但只有一种疗法（低潮气量通气）已被证明可降低ARDS的死亡率。对这种毁灭性疾病发病机制的进一步研究对于开发针对特定疾病机制的新型特异性疗法至关重要。不幸的是，没有一种ARDS动物模型能复制患者中所见的复杂病理生理变化。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。在此，我们讨论该综合征的主要特征，强调当前动物模型的局限性，并提出研究发病机制关键组成部分的新方法。希望随着新技术和方法的出现，ARDS科学进展的障碍将被克服。
