Decreased pulmonary extracellular superoxide dismutase during systemic inflammation
Decreased pulmonary extracellular superoxide dismutase during systemic inflammation
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DOI：
10.1016/j.freeradbiomed.2008.06.016
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发表时间：
2008-09-15
影响因子：
7.4
通讯作者：
Saito, Hiroshi
中科院分区：
文献类型：
--
作者：
Ueda, Junji;Starr, Marlene E.;Saito, Hiroshi
氧化损伤是全身炎症反应综合征时肺损伤的主要原因。在这项研究中，抗氧化酶，细胞外超氧化物歧化酶（EC-SOD）的表达及其对肺氧化损伤的保护作用，使用小鼠全身炎症模型进行了研究。腹腔注射细菌内毒素脂多糖（LPS; 20 mg/kg）引起肺氧化损伤，通过蛋白质酪氨酸硝化增加进行评估。LPS也导致肺EC-SOD的80%以上的快速和显着的损失，在时间和剂量依赖性的方式，但其他类型的SOD，细胞质CuZn-SOD和线粒体Mn-SOD没有受到影响。EC-SOD蛋白在肺中最丰富，但在其他组织如心脏和白色脂肪中也以高水平存在：然而，LPS介导的这种酶的减少在肺中最明显。小鼠静脉注射肿瘤坏死因子α（每只小鼠10 μ g）也导致肺中EC-SOD下降60%，表明EC-SOD下调是由这种LPS诱导的炎性细胞因子介导的。EC-SOD对LPS介导的全身性炎症的保护作用表现为在过表达人EC-SOD基因的EC-SOD转基因小鼠中增加的存活率（5天内75%对29%）和减少的肺氧化损伤。这些结果表明，炎症介导的EC-SOD下调在全身炎症反应综合征中具有重要的病理生理影响。(C)2008年爱思唯尔公司All rights reserved.
Oxidative damage is a major cause Of lung injury during systemic inflammatory response syndrome. In this Study, the expression of an antioxidant enzyme, extracellular superoxide dismutase (EC-SOD) and its, protective role against Pulmonary oxidative damage were investigated using Mouse models of systemic inflammation. Intraperitoneal injection with bacterial endotoxin lipopolysaccharides (LPS; 20 mg/kg) caused oxidative damage in lungs as assessed by increased tyrosine nitration in proteins. LPS administration also resulted in a rapid and significant loss of more than 80% of pulmonary EC-SOD in a time- and dose-dependent manner, but other types of SODs, cytoplasmic CuZn-SOD and mitochondrial Mn-SOD were not, affected. EC-SOD protein is most abundant in lungs but also present at high levels in other tissues such as heart and white fat: however, the LPS-mediated decrease in this enzyme was most apparent in the lungs. Intravenous injection of mice with tumor necrosis factor alpha (10 mu g per mouse) also caused a 60% decrease in EC-SOD in the lungs, suggesting that the EC-SOD down-regulation is mediated by this LPS-inducible inflammatory cytokine. A protective role for EC-SOD against LPS-mediated systemic inflammation was shown by an increased survival rate (75% vs 29% in 5 days) and decreased pulmonary oxidative damage in EC-SOD transgenic mice that overexpress the human EC-SOD gene. These results demonstrate that the inflammation-mediated EC-SOD down-regulation has a major pathophysiological impact during the systemic inflammatory response syndrome. (C) 2008 Elsevier Inc. All rights reserved.