Wurfel Mark M
Division of Pulmonary and Critical Care Medicine, Harborview Medical Center, University of Washington, Seattle, Washington 98104, USA.
Proc Am Thorac Soc. 2007 Jan;4(1):77-84. doi: 10.1513/pats.200608-149JG.
Acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) are a frequent cause of intensive care unit admission, affecting over 200,000 patients in the United States each year. Mechanical ventilation is a life-saving intervention in the setting of ARDS and ALI, but clinical trials have demonstrated that mechanical ventilation with excessive tidal volumes plays a role in promoting and perpetuating lung injury and leads to excess mortality. This process has been labeled ventilator-induced lung injury (VILI), but the molecular mechanisms driving this process and its interactions with predisposing risk factors such as sepsis and chemical injury remain incompletely understood. Genome-wide measurements of gene expression using microarray technology represent a powerful tool to examine the pathophysiology of VILI. Several recent studies have used this approach to study VILI in isolation and associated with endotoxin instillation or saline lavage. These studies and others examining gene expression profiles in epithelial cells subjected to cyclic stretch have provided novel insights on the molecular mechanisms underlying VILI. This review will summarize these findings and discuss implications for future studies.
急性呼吸窘迫综合征(ARDS)和急性肺损伤(ALI)是重症监护病房收治患者的常见病因,在美国每年影响超过200,000名患者。机械通气是ARDS和ALI情况下的一种挽救生命的干预措施,但临床试验表明,大潮气量机械通气在促进和延续肺损伤中起作用,并导致额外的死亡率。这个过程被称为呼吸机诱导的肺损伤(VILI),但驱动这个过程的分子机制及其与脓毒症和化学损伤等易感危险因素的相互作用仍未完全了解。使用微阵列技术进行全基因组基因表达测量是研究VILI病理生理学的有力工具。最近的几项研究使用这种方法单独研究VILI,并与内毒素注入或盐水灌洗相关联。这些研究以及其他研究在经历周期性拉伸的上皮细胞中检查基因表达谱,为VILI的分子机制提供了新的见解。本综述将总结这些发现并讨论对未来研究的意义。