Different gene expression patterns in acute lung injury

抄録

Background: Acute lung injury (ALI) is one of the most severe clinical situations associated with major surgical procedures. Although prolonging-time of mechanical ventilation (MV) is required for these patients, MV itself can worsen preexisting lung injury. Moreover, Hemorrhagic shock (HS) and endotoxiemia (LPS) can be fatal to patients who are on MV. In the present study, we explored the hypothesis that ALI secondary to different stimuli could be distinguished based on the pattern of gene expression.Methods: Rats received hemorrhagic or endotoxic shock followed by resuscitation, or sham operation. They were randomized to either high (12 ml/kg) or low (6 ml/kg) volume ventilation of 4 hours. Blood gas and lung elastance were measured during MV. Lung injury was assessed by wet/dry lung ratio and histological examination. RNA samples were examined with Affymetrix rat microarray chips and real-time RT-PCR. Results: After 4 hours of MV, animals with HS or LPS in high volume ventilation groups showed significantly lower PaO2 levels, increased elastance and lung wet/dry ratios, compared with animals in low volume ventilation groups. However, no differences were found between HS and LPS groups. In contrast, Microarray analysis revealed different gene profiles between HS and LPS groups. Two groups of genes were selected and further confirmed by real-time RT-PCR. Conclusion: The underlying molecular mechanisms are very different. Therefore, genes identified by the bioinformatics approach could provide potential biomarkers to differentiate ALI due to a variety of etiologies.