Investigational Intensive Care Unit, Department of Anesthesiology, University of Texas Medical Branch, Galveston, Texas 77550, USA.
Shock. 2012 May;37(5):468-72. doi: 10.1097/SHK.0b013e31824b1793.
The formation of oxidative stress in the lung and activation of neutrophils are major determinants in the development of respiratory failure after acute lung injury and sepsis. However, the time changes of these pathogenic factors have not been sufficiently described. Twenty-four chronically instrumented sheep were subjected to cotton smoke inhalation injury and instillation of live Pseudomonas aeruginosa into both lungs. The sheep were euthanized at 4, 8, 12, 18, and 24 h after injury. Additional sheep received sham injury and were euthanized after 24 h. Pulmonary function was assessed by determination of oxygenation index and pulmonary shunt fraction. In addition, lung tissue was harvested at the respective time points for the measurement of malondialdehyde, interleukin 6, poly(ADP ribose), myeloperoxidase, and alveolar polymorphonuclear neutrophil score. The injury induced severe respiratory failure that was associated with an early increase in lipid peroxidation and interleukin 6 expression. The injury further led to an increase in poly(ADP ribose) activity that reached its peak at 12 h after injury and declined afterward. In addition, progressive increases in markers of neutrophil accumulation in the lung were observed. The peak of neutrophil accumulation in the lung was associated with a severe depletion of circulating neutrophils. The results from our model may enhance the understanding of the pathophysiological alterations after acute lung injury and sepsis and thus be useful in exploring therapeutic interventions directed at modifying the expression or activation of inflammatory mediators.
肺部氧化应激的形成和中性粒细胞的激活是急性肺损伤和脓毒症后呼吸衰竭发展的主要决定因素。然而，这些致病因素的时间变化尚未得到充分描述。24 只接受慢性仪器植入的绵羊接受棉烟吸入性损伤和活铜绿假单胞菌注入双肺。损伤后 4、8、12、18 和 24 小时处死绵羊。另外一些绵羊接受假损伤，并在 24 小时后处死。通过测定氧合指数和肺分流分数评估肺功能。此外，在相应时间点采集肺组织，测量丙二醛、白细胞介素 6、多聚（ADP 核糖）、髓过氧化物酶和肺泡多形核中性粒细胞评分。损伤导致严重呼吸衰竭，与脂质过氧化和白细胞介素 6 表达的早期增加有关。损伤进一步导致多聚（ADP 核糖）活性增加，在损伤后 12 小时达到峰值，随后下降。此外，还观察到肺内中性粒细胞积聚标志物的逐渐增加。肺内中性粒细胞积聚的峰值与循环中性粒细胞的严重耗竭有关。我们的模型结果可能会增强对急性肺损伤和脓毒症后病理生理改变的理解，从而有助于探索针对炎症介质表达或激活的治疗干预措施。
