Signaling of apoptotic lung injury by liquid hydroperoxides
Signaling of apoptotic lung injury by liquid hydroperoxides
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DOI：
10.1097/00005373-199805000-00007
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发表时间：
1998-05-01
影响因子：
--
通讯作者：
Dulchavsky, SA
中科院分区：
文献类型：
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作者：
Compton, CN;Franko, AP;Dulchavsky, SA
背景：急性肺损伤常见于休克和败血症后，但其病理生理机制尚不清楚。脂质过氧化氢产物包括4-羟基壬烯醛（HNE）在这些损伤中显著增加，并可能诱导细胞凋亡。本研究探讨HNE病理生理浓度对离体肺生物物理功能和细胞凋亡的影响。方法：雄性sd - dawley大鼠肺分离，用Krebs-Henseleit缓冲液灌注120分钟，灌注60分钟时加入羟基烯醛（50 μ mol/L）或对照物。测定肺弹性和灌注压。每隔30分钟测定灌注谷胱甘肽和乳酸脱氢酶。提取基因组DNA，电泳测定细胞凋亡阶梯。结果：两组在HNE输注前各项指标均无差异。HNE输注组肺水肿明显增加；肺弹性和灌注压有增加的趋势。细胞凋亡的DNA阶梯特征在hne处理的肺中被注意到，而在对照动物中没有。结论：休克或败血症时形成的脂质过氧化氢产物可能与肺损伤有因果关系。低浓度的候选代谢物HNE似乎会诱导显著的肺损伤和细胞凋亡，这可能部分介导休克和败血症期间的肺损伤。
Background: Acute lung injury is common after shock and sepsis, but the pathophysiology is unclear. Lipid hydroperoxide products including 4-hydroxynonenal (HNE) increase significantly during these insults and may induce apoptosis. This study investigates the role of pathophysiologic concentrations of HNE on isolated lung biophysical function and apoptosis.Methods: Male Sprague-Dawley rat lungs were isolated and perfused with Krebs-Henseleit buffered solution for 120 minutes, Hydroxynonenal (50 mu mol/L) or vehicle was added to the perfusate at 60 minutes. Lung elastance and perfusion pressure were determined. Perfusate glutathione and lactate dehydrogenase were determined at 30-minute intervals. Genomic DNA was extracted for electrophoretic determination of apoptotic laddering.Results: There were no differences in any parameter measured before HNE infusion. Lung edema increased significantly with HNE infusion; a trend increase in lung elastance and perfusion pressure was noted. DNA laddering characteristic of apoptosis was noted in HNE-treated lungs that was absent in control animals.Conclusion: Lipid hydroperoxide products formed during shock or sepsis may be causally related to lung injury. Low concentrations of a candidate metabolite, HNE, appear to induce significant lung injury and apoptosis, which may partially mediate lung injury during shock and sepsis.