Hyperoxia exposure alters hepatic eicosanoid metabolism in newborn mice.
Hyperoxia exposure alters hepatic eicosanoid metabolism in newborn mice.
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DOI：
10.1203/pdr.0b013e3181c2df4f
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发表时间：
2010-02
影响因子：
3.6
通讯作者：
Welty SE
中科院分区：
文献类型：
--
作者：
Rogers LK;Tipple TE;Britt RD;Welty SE
早产儿通常使用超生理量的氧气进行治疗，这与肺损伤和支气管肺发育不良等疾病的发展有关。在高氧肺损伤过程中，肺和肝之间的互补反应已在成年动物中进行了研究，但对新生儿中的这种关系知之甚少。这些研究验证了以下假设：新生小鼠的肝脏对持续高氧暴露作出反应时发生氧化应激。暴露于高氧的新生小鼠的肺组织中检测到谷胱甘肽二硫化物和硝基酪氨酸的水平高于暴露于室内空气的对照组，但未检测到肝组织。然而，早期增加5-脂氧合酶和环氧合酶-2蛋白水平和总羟基二十碳四烯酸和前列腺素水平的增加，观察到在高氧暴露的幼崽的肝组织。这些研究表明，自由基氧化发生在新生幼崽暴露于高氧肺，脂质代谢的改变可能是在肝组织的主要反应。本研究的发现确定了新生儿支气管肺发育不良模型中与高氧肺损伤相关的可能的新机制，从而为研究提供了机会。
Prematurely born infants are often treated with supraphysiologic amounts of oxygen, which is associated with lung injury and the development of diseases such as bronchopulmonary dysplasia. Complimentary responses between the lung and liver during the course of hyperoxic lung injury have been studied in adult animals, but little is known about this relationship in neonates. These studies tested the hypothesis that oxidant stress occurs in the livers of newborn mice in response to continuous hyperoxia exposure. Greater levels of glutathione disulfide and nitrotyrosine were detected in lung tissues but not liver tissues from newborn mice exposed to hyperoxia than in room air-exposed controls. However, early increases in 5-lipoxygenase and cyclooxygenases-2 protein levels and increases in total hydroxyeicosatetraenoic acid and prostaglandin levels were observed in the liver tissues of hyperoxia-exposed pups. These studies indicate that free radical oxidation occurs in the lungs of newborn pups exposed to hyperoxia, and alterations in lipid metabolism could be a primary response in the liver tissues. The findings of this study identify possible new mechanisms associated with hyperoxic lung injury in a newborn model of bronchopulmonary dysplasia and thus open opportunities for research.