Jean Mayer United States Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA.
J Appl Physiol (1985). 2012 Apr;112(7):1184-90. doi: 10.1152/japplphysiol.01334.2011. Epub 2012 Feb 2.
Oxidative damage has been said to play an important role in pulmonary injury, which is associated with the development and progression of acute respiratory distress syndrome (ARDS). We aimed to identify biomarkers to determine the oxidative stress in an animal model of acute lung injury (ALI) using two different strategies of mechanical ventilation. Rabbits were ventilated using either conventional mechanical ventilation (CMV) or high-frequency oscillatory ventilation (HFOV). Lung injury was induced by tracheal saline infusion (30 ml/kg, 38°C). In addition, five healthy rabbits were studied for oxidative stress. Isolated lymphocytes from peripheral blood and lung tissue samples were analyzed by alkaline single cell gel electrophoresis (comet assay) to determine DNA damage. Total antioxidant performance (TAP) assay was applied to measure overall antioxidant performance in plasma and lung tissue. HFOV rabbits had similar results to healthy animals, showing significantly higher antioxidant performance and lower DNA damage compared with CMV in lung tissue and plasma. Total antioxidant performance showed a significant positive correlation (r = 0.58; P = 0.0006) in plasma and lung tissue. In addition, comet assay presented a significant positive correlation (r = 0.66; P = 0.007) between cells recovered from target tissue and peripheral blood. Moreover, antioxidant performance was significantly and negatively correlated with DNA damage (r = -0.50; P = 0.002) in lung tissue. This study indicates that both TAP and comet assay identify increased oxidative stress in CMV rabbits compared with HFOV. Antioxidant performance analyzed by TAP and oxidative DNA damage by comet assay, both in plasma, reflects oxidative stress in the target tissue, which warrants further studies in humans.
氧化损伤被认为在肺损伤中起重要作用，肺损伤与急性呼吸窘迫综合征（ARDS）的发生和发展有关。我们旨在使用两种不同的机械通气策略，在急性肺损伤（ALI）动物模型中确定生物标志物以确定氧化应激。兔子使用常规机械通气（CMV）或高频振荡通气（HFOV）进行通气。肺损伤通过气管盐水输注（30ml/kg，38°C）诱导。此外，还对 5 只健康兔子进行了氧化应激研究。通过碱性单细胞凝胶电泳（彗星试验）分析外周血和肺组织样本中的分离淋巴细胞，以确定 DNA 损伤。应用总抗氧化能力（TAP）测定法测量血浆和肺组织中的总抗氧化能力。HFOV 兔子与健康动物的结果相似，与 CMV 相比，肺组织和血浆中的抗氧化性能明显更高，DNA 损伤明显更低。总抗氧化能力在血浆和肺组织中呈显著正相关（r=0.58；P=0.0006）。此外，彗星试验显示，从靶组织和外周血中回收的细胞之间存在显著正相关（r=0.66；P=0.007）。此外，抗氧化性能与肺组织中的 DNA 损伤呈显著负相关（r=-0.50；P=0.002）。本研究表明，与 HFOV 相比，TAP 和彗星试验均表明 CMV 兔子的氧化应激增加。TAP 分析的总抗氧化能力和彗星试验的氧化 DNA 损伤，无论是在血浆中还是在靶组织中，都反映了氧化应激，这需要在人类中进一步研究。
