首页> 外文期刊>American Journal of Physiology >Role of TNF-a-induced reactive oxygen species in endothelial dysfunction during reperfusion injury
【24h】

Role of TNF-a-induced reactive oxygen species in endothelial dysfunction during reperfusion injury

机译:TNF-α诱导的活性氧在再灌注损伤中内皮功能障碍中的作用

获取原文
获取原文并翻译 | 示例
           

摘要

Role of TNF-a-induced reactive oxygen species in endothelial dysfunction during reperfusion injury. Am J Physiol Heart Circ Phys-iol 295: H2242-H2249, 2008. First published October 10, 2008; doi:10.1152/ajpheart.00587.2008.俥 hypothesized that neutralization of TNF-a at the time of reperfusion exerts a salubrious role on endothelial function and reduces the production of reactive oxygen species. We employed a mouse model of myocardial ischemia-reperfusion (I/R, 30 min/90 min) and administered TNF-a neutralizing antibodies at the time of reperfusion. I/R elevated TNF-a expression (mRNA and protein), whereas administration of anti-TNF-a before reperfusion attenuated TNF-a expression. We detected TNF-a expression in vascular smooth muscle cells, mast cells, and macrophages, but not in the endothelial cells. I/R induced endothelial dysfunction and superoxide production. Administration of anti-TNF-a at the onset of reperfusion partially restored nitric oxide-mediated coronary arteriolar dilation and reduced superoxide production. I/R increased the activity of NAD(P)H oxidase and of xanthine oxidase and enhanced the formation of nitrotyrosine residues in untreated mice compared with shams. Administration of anti-TNF-a before reperfusion blocked the increase in activity of these enzymes. Inhibition of xanthine oxidase (allopurinol) or NAD(P)H oxidase (apocynin) improved endothelium-dependent dilation and reduced superoxide production in isolated coronary arterioles following I/R. Interestingly, I/R enhanced superoxide generation and reduced endothelial function in neutropenic animals and in mice treated with a neutrophil NAD(P)H oxidase inhibitor, indicating that the effects of TNF-a are not through neutrophil activation. We conclude that myocardial ischemia initiates TNF-a "expression, which induces vascular oxidative stress, independent of neutrophil activation, and leads to coronary endothelial dysfunction
机译:TNF-α诱导的活性氧在再灌注损伤过程中内皮功能障碍中的作用。 Am J Physiol Heart Circ Phys-iol 295:H2242-H2249,2008年。2008年10月10日首次发布。 doi:10.1152 / ajpheart.00587.2008。俥假定再灌注时中和TNF-a对内皮功能起有益作用,并减少了活性氧的产生。我们采用了心肌缺血-再灌注的小鼠模型(I / R,30分钟/ 90分钟),并在再灌注时给予了TNF-a中和抗体。 I / R升高了TNF-α的表达(mRNA和蛋白质),而在再灌注前给予抗TNF-α则减弱了TNF-α的表达。我们在血管平滑肌细胞,肥大细胞和巨噬细胞中检测到TNF-a表达,但在内皮细胞中未检测到。 I / R诱导的内皮功能障碍和超氧化物生成。在再灌注开始时给予抗TNF-α可以部分恢复一氧化氮介导的冠状动脉扩张并减少超氧化物的产生。 I / R增加了未处理小鼠的NAD(P)H氧化酶和黄嘌呤氧化酶的活性,并增强了硝基酪氨酸残基的形成。在再灌注前施用抗TNF-α阻止了这些酶活性的增加。黄嘌呤氧化酶(allopurinol)或NAD(P)H氧化酶(apocynin)的抑制作用改善了I / R后分离的冠状小动脉中内皮依赖性的扩张并降低了超氧化物的产生。有趣的是,I / R在嗜中性白血球减少和中性粒细胞NAD(P)H氧化酶抑制剂治疗的小鼠中增强了超氧化物的生成并降低了内皮功能,这表明TNF-α的作用不是通过中性粒细胞的活化。我们得出结论,心肌缺血会启动“ TNF-a”的表达,从而诱导血管氧化应激,独立于中性粒细胞的活化,并导致冠状动脉内皮功能障碍

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号