Inhaled nitric oxide protects against hyperoxia-induced apoptosis in rat lungs
Inhaled nitric oxide protects against hyperoxia-induced apoptosis in rat lungs
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DOI：
10.1152/ajplung.1999.277.3.l596
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发表时间：
1999-09-01
影响因子：
4.9
通讯作者：
Fliss, H
中科院分区：
文献类型：
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作者：
Howlett, CE;Hutchison, JS;Fliss, H
吸入一氧化氮(NO)，经常与高氧混合气体一起使用，最近被证明可以防止长期高氧的有害后果。我们研究了这种保护作用可能归因于NO阻止肺细胞凋亡的能力。我们发现，暴露在100%O2中60h的大鼠发生了严重的肺损伤，包括明显的血管渗漏和肺泡细胞凋亡，这是因为琼脂糖凝胶中存在末端脱氧核苷酸转移酶介导的dUTP缺口、末端标记和DNA梯状条带，以及结构性proaspase-3水平的下降。然而，在高氧混合气中加入20份/百万份的NO显著减少了血管泄漏和细胞凋亡。NO可逆转氧化还原敏感的转录因子核因子-kappaB、激活蛋白-1和Sp1在高氧作用下的活性变化，降低细胞间黏附分子-1水平，增加谷胱甘肽含量。因此，我们首次发现，NO可以保护细胞免受高氧诱导的细胞凋亡和炎症。数据表明，这种保护可能发生在转录和caspase激活水平。
Inhaled nitric oxide (NO), frequently administered in combination with hyperoxic gas mixtures, was recently shown to protect against the injurious consequences of prolonged hyperoxia. We investigated the possibility that this protective effect is attributable to the ability of NO to block pulmonary apoptosis. We show that rats exposed to 100% O-2 for 60 h develop severe lung injury consisting of pronounced vascular leak and alveolar apoptosis as inferred from the presence of positive terminal deoxynucleotidyltransferase-mediated dUTP nick, end labeling and DNA ladders in agarose gels and a decrease in constitutive procaspase-3 levels. However, the inclusion of NO (20 parts/million) in the hyperoxic gas mixture significantly attenuated both the vascular leak and apoptosis. NO reversed the hyperoxia-associated changes in the activity of the redox-sensitive transcription factors nuclear factor-kappa B, activator protein-1, and Sp1 after 24 h, lowered intercellular adhesion molecule-1 levels, and increased glutathione content. We therefore show, for the first time, that NO can protect against both hyperoxia-induced apoptosis and inflammation. The data suggest that this protection may occur at the transcriptional and caspase-activation levels.