Alda-1通过降低肺泡上皮内的4-羟基壬烯醛而减轻肺部再灌注损伤

Alda-1 attenuates lung ischemia-reperfusion injury by reducing 4-hydroxy-2-nonenal in alveolar epithelial cells
2016-10-06 08:09发表评论
作者:Ding, J., Zhang, Q., Luo, Q., Ying, Y., Liu, Y., Li, Y., Wei, W., Yan, F. , Zhang, H.
机构: 北京协和医院阜外医院,国家心血管病中心
期刊: Crit Care2016年7月7期44卷

Objectives: Excessive oxidative stress is a main cause of lung ischemia-reperfusion injury, which often results in respiratory insufficiency after open-heart surgery for a cardiopulmonary bypass. Previous studies demonstrate that the activation of aldehyde dehydrogenase-2 could significantly reduce the oxidative stress mediated by toxic aldehydes and attenuate cardiac and cerebral ischemia-reperfusion injury. However, both the involvement of aldehydes and the protective effect of the aldehyde dehydrogenase-2 agonist, Alda-1, in lung ischemia-reperfusion injury remain unknown. Design: Prospective laboratory and animal investigation were conducted. Setting: State Key Laboratory of Cardiovascular Disease. Subjects: Primary human pulmonary alveolar epithelial cells, human pulmonary microvascular endothelial cells, and Sprague-Dawley rats. Interventions: A hypoxia/reoxygenation cell-culture model of human pulmonary alveolar epithelial cell, human pulmonary microvascular endothelial cell, and an isolated-perfused lung model were applied to mimic lung ischemia-reperfusion injury. We evaluated the effects of Alda-1 on aldehyde dehydrogenase-2 quantity and activity, on aldehyde levels and pulmonary protection. Measurements and Main Results: We have demonstrated that ischemia-reperfusion-induced pulmonary injury concomitantly induced aldehydes accumulation in human pulmonary alveolar epithelial cells and lung tissues, but not in human pulmonary microvascular endothelial cells. Moreover, Alda-1 pretreatment significantly elevated aldehyde dehydrogenase-2 activity, increased surfactant-associated protein C, and attenuated elevation of 4-hydroxy-2-nonenal, apoptosis, intercellular adhesion molecule-1, inflammatory response, and the permeability of pulmonary alveolar capillary barrier, thus alleviated injury. Conclusions: Our study indicates that the accumulation of 4-hydroxy-2-nonenal plays an important role in lung ischemia-reperfusion injury. Alda-1 pretreatment can attenuate lung ischemia-reperfusion injury, possibly through the activation of aldehyde dehydrogenase-2, which in turn removes 4-hydroxy-2-nonenal in human pulmonary alveolar epithelial cells. Alda-1 pretreatment has clinical implications to protect lungs during cardiopulmonary bypass.

© 2016 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc.

通讯机构: Fuwai Hospital, National Center of Cardiovascular Diseases, Peking Union Medical College, Beijing, China
学科代码:急诊医学 重症监护   关键词:Alda-1 肺泡上皮 4-羟基壬烯醛 ,中国作者重要发表 爱思唯尔医学网, Elseviermed
来源: Scopus
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