Dexamethasone treatment in the newborn rat: fatty acid profiling of lung, brain, and serum lipids.

Dexamethasone treatment in the newborn rat: fatty acid profiling of lung, brain, and serum lipids.
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DOI:
10.1152/japplphysiol.01029.2004
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发表时间:
2005-03
影响因子:
3.3
通讯作者:
E. Bruder;P. Lee;H. Raff
E. Bruder;P. Lee;H. Raff
中科院分区:
医学2区
文献类型:
--
作者:
E. Bruder;P. Lee;H. Raff

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地塞米松可用于治疗多种新生儿综合症,包括呼吸窘迫。本研究利用全面脂质分析的能力来表征与地塞米松治疗相关的新生儿肺和脑中脂质代谢的变化,并确定地塞米松与缺氧的相互作用。在出生后第3天(0.5 mg/kg)、第4天(0.25 mg/kg)、第5天(0.125 mg/kg)和第6天(0.05 mg/kg),于0800给予地塞米松4天逐渐减量方案。一个亚组的大鼠从出生到7日龄暴露于缺氧。地塞米松治疗引起了许多特定的变化,在含氧量正常的肺的脂质,如磷脂酰胆碱和胆固醇酯类的饱和脂肪酸浓度增加。这些增加在缺氧幼鼠的肺中更为深刻。在用地塞米松处理的缺氧幼鼠的肺中也测量到心磷脂浓度的额外增加。我们测量了地塞米松治疗后血脂的广泛增加,但在常氧和缺氧的幼崽之间的效果是不相等的。地塞米松治疗在缺氧的幼崽增加20:4 n6和22:6 n3浓度的游离脂肪酸类的大脑。我们的研究结果表明,地塞米松治疗新生儿eleclamped特定的肺脂质代谢的变化与表面活性剂的生产,独立的血脂变化。这些发现说明了地塞米松对肺功能的益处,但也增加了高脂血症和脑脂质代谢微妙变化造成负面影响的可能性。
Dexamethasone is used as treatment for a variety of neonatal syndromes, including respiratory distress. The present study utilized the power of comprehensive lipid profiling to characterize changes in lipid metabolism in the neonatal lung and brain associated with dexamethasone treatment and also determined the interaction of dexamethasone with hypoxia. A 4-day tapering-dose regimen of dexamethasone was administered at 0800 on postnatal days 3 (0.5 mg/kg), 4 (0.25 mg/kg), 5 (0.125 mg/kg), and 6 (0.05 mg/kg). A subgroup of rats was exposed to hypoxia from birth to 7 days of age. Dexamethasone treatment elicited numerous specific changes in the lipid profile of the normoxic lung, such as increased concentrations of saturated fatty acids in the phosphatidylcholine and cholesterol ester classes. These increases were more profound in the lungs of hypoxic pups. Additional increases in cardiolipin concentrations were also measured in lungs of hypoxic pups treated with dexamethasone. We measured widespread increases in serum lipids after dexamethasone treatment, but the effects were not equivalent between normoxic and hypoxic pups. Dexamethasone treatment in hypoxic pups increased 20:4n6 and 22:6n3 concentrations in the free fatty acid class of the brain. Our results suggest that dexamethasone treatment in neonates elicits specific changes in lung lipid metabolism associated with surfactant production, independent of changes in serum lipids. These findings illustrate the benefits of dexamethasone on lung function but also raise the potential for negative effects due to hyperlipidemia and subtle changes in brain lipid metabolism.