期刊
CRITICAL CARE MEDICINE
卷 44, 期 7, 页码 E544-E552出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/CCM.0000000000001563
关键词
4-hydroxy-2-nonenal; alda-1; epithelial cells; lung injury; pulmonary alveoli; reperfusion injury
资金
- National Nature Science Foundation of China [81270225, 81370187]
- Program for New Century Excellent Talents in University
- Innovative Foundation for Graduate Students at Peking Union Medical College [10023-1002-3002]
- innovative foundation for Graduate Students of Peking Union Medical College [10023-1002-3002]
- National Natural Scientific Foundation of China [81270225]
- National Natural Scientific Foundation of China
- foundation for talent in new century
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.
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