Changes in plasma gelsolin concentration during acute oxidant lung injury in mice
Changes in plasma gelsolin concentration during acute oxidant lung injury in mice
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DOI：
10.1007/s004080000084
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发表时间：
2002-03-01
期刊：
影响因子：
5
通讯作者：
DiNubile, MJ
中科院分区：
文献类型：
--
作者：
Christofidou-Solomidou, M;Scherpereel, A;DiNubile, MJ
氧化应激在某些情况下可导致急性肺损伤。严重创伤后发生呼吸窘迫的患者血浆凝胶的迅速耗竭表明，这种肌动蛋白清除蛋白可能防止延迟性肺部并发症。这些实验的具体目的是探讨凝胶水平与肺损伤之间的时间和定量关系。在三种小鼠氧化损伤模型中测定Gelsolin水平：用h2o2生成酶免疫靶向肺内皮；连续暴露于> 95% O-2；以及单次高剂量胸部放射。葡萄糖氧化酶偶联抗血小板内皮细胞粘附分子-1抗体处理小鼠的肺损伤程度与凝胶水平呈负相关（p < 0.0001）。高氧暴露60-72小时后，所有肺损伤小鼠的凝胶水平急剧下降（p < 0.0001）。建立凝胶浓度与高氧肺损伤之间的定量关联（r = -0.72； 95%可信区间：-0.81 ~ -0.59）。在治疗后的3天内，辐照小鼠的Gelsolin水平适度但逐渐下降（p = 0.012），尽管在此期间仅发生了微小的肺损伤。这些发现与gelsolin耗竭参与急性氧化性肺损伤发病机制的假设一致。
Oxidant stress may contribute to acute lung injury under some circumstances. The rapid depletion of plasma gelsolin following major trauma in patients who subsequently develop respiratory distress suggests that this actin-scavenging protein might protect against delayed pulmonary complications. The specific aim of these experiments was to explore the temporal and quantitative relationship between gelsolin levels and lung damage. Gelsolin levels were measured in three murine models of oxidant injury: immunotargeting of pulmonary endothelium with an H2O2-generating enzyme; continuous exposure to > 95% O-2; and single high-dose thoracic radiation. The degree of lung injury was inversely related to gelsolin levels in mice treated with glucose oxidase-conjugated antibodies against platelet endothelial cell adhesion molecule-1 (p < 0.0001). By 60-72 hours of hyperoxic exposure, gelsolin levels had dropped precipitously in all mice who sustained major lung damage (p < 0.0001). establishing a quantitative association between gelsolin concentration and hyperoxic lung injury (r = -0.72; 95% confidence interval: -0.81 to -0.59). Gelsolin levels modestly but progressively fell in irradiated mice over the 3 days following treatment(p = 0.012) despite the development of only microscopic lung damage during this timeframe. These findings are consistent with the hypothesis that gelsolin depletion is involved in the pathogenesis of acute oxidant lung injury.