Extracellular superoxide dismutase attenuates lung injury after hemorrhage

被引:52
作者
Bowler, RP
Arcaroli, J
Crapo, JD
Ross, A
Slot, JW
Abraham, E
机构
[1] Natl Jewish Med & Res Ctr, Denver, CO 80206 USA
[2] Univ Colorado, Hlth Sci Ctr, Div Pulm Sci & Crit Care Med, Denver, CO USA
[3] Univ Utrecht, Dept Pathol, Utrecht, Netherlands
关键词
hemorrhage; extracellular superoxide dismutase; NF-kappa B; myeloperoxidase;
D O I
10.1164/ajrccm.164.2.2011054
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
Reperfusion of the lung after hemorrhage generates free radicals such as superoxide (O-2') that may injure the lung; however, the relative importance of intracellular versus extracellular free radicals is unclear. The superoxide dismutases (SOD) are the primary enzymatic method to reduce superoxide. We examined whether lung-specific overexpression of extracellular superoxide dismutase (EC-SOD) would attenuate hemorrhage-induced lung injury. Wildtype mice and mice overexpressing the human EC-SOD gene with a lung-specific promoter were hemorrhaged by removing 30% of blood volume. After hemorrhage, the lung wet to dry weight ratios increased from 5.4 +/- 0.11 in unmanipulated control mice to 6.3 +/- 0.16 in wild-type mice, but to only 5.60 +/- 0.17 in the EC-SOD transgenic mice (p < 0.05 compared with hemorrhaged wildtype). Hemorrhage-induced lipid peroxidation, as assessed by lung F-2 isoprostanes, was lower in the EC-SOD transgenic mice (3.4 +/- 0.3 mug/lung) compared with wild-type mice (1.9 +/- 0.2 mug/lung; p < 0.05). Compared with wild-type, EC-SOD transgenic mice had attenuated the hemorrhage-induced increase in both pulmonary nuclear factor kappa B (NK-kappaB) activation (relative absorbance 1.1 +/- 0.2 for EC-SOD transgenic versus 2.5 +/- 0.1 for wild-type; p < 0.05) and myeloperoxidase activity (5.1 +/- 0.87 units/g for EC-SOD transgenic versus 11.3 +/- 1.8 units/g for wild-type; p < 0.01). Thus, overexpression of pulmonary EC-SOD in the mouse lung attenuates lung injury after hemorrhage.
引用
收藏
页码:290 / 294
页数:5
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