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母体产前补充ω-3脂肪酸可减轻高氧诱导的发育中大鼠大脑细胞凋亡。

Maternal prenatal omega-3 fatty acid supplementation attenuates hyperoxia-induced apoptosis in the developing rat brain.

作者信息

Tuzun Funda, Kumral Abdullah, Ozbal Seda, Dilek Mustafa, Tugyan Kazım, Duman Nuray, Ozkan Hasan

机构信息

Department of Neonatology, School of Medicine, Dokuz Eylul University, Turkey.

出版信息

Int J Dev Neurosci. 2012 Jun;30(4):315-23. doi: 10.1016/j.ijdevneu.2012.01.007. Epub 2012 Jan 28.

Abstract

Supraphysiologic amounts of oxygen negatively influences brain maturation and development. The aim of the present study was to evaluate whether maternal ω-3 long-chain polyunsaturated fatty acid (ω-3 FA) supplementation during pregnancy protects the developing brain against hyperoxic injury. Thirty-six rat pups from six different dams were divided into six groups according to the diet modifications and hyperoxia exposure. The groups were: a control group (standard diet+room air), a hyperoxia group (standard diet+80% O₂ exposure), a hyperoxia+high-dose ω-3 FA-supplemented group, a hyperoxia+low-dose ω-3 FA-supplemented group, a room air+low-dose ω-3 FA-supplemented+group, and a room air+high dose ω-3 FA-supplemented group. The ω-3 FA's were supplemented as a mixture of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) from the second day of pregnancy until birth. Rat pups in the hyperoxic groups were exposed to 80% oxygen from birth until postnatal day 5 (P5). At P5, all animals were sacrificed. Neuronal cell death and apoptosis were evaluated by cell count, TUNEL, and active Caspase-3 immunohistochemistry. Histopathological examination showed that maternally ω-3 FA deficient diet and postnatal hyperoxia exposure were associated with significantly lower neuronal counts and significantly higher apoptotic cell death in the selected brain regions. Ω-3 FA treatment significantly diminished apoptosis, in the selected brain regions, in a dose dependent manner. Our results suggest that the maternal ω-3 FA supply may protect the developing brain against hyperoxic injury.

摘要

超生理量的氧气会对大脑成熟和发育产生负面影响。本研究的目的是评估孕期补充母体ω-3长链多不饱和脂肪酸(ω-3 FA)是否能保护发育中的大脑免受高氧损伤。将来自6只不同母鼠的36只幼鼠根据饮食改变和高氧暴露情况分为6组。这些组分别是:对照组(标准饮食+室内空气)、高氧组(标准饮食+80%氧气暴露)、高氧+高剂量ω-3 FA补充组、高氧+低剂量ω-3 FA补充组、室内空气+低剂量ω-3 FA补充组和室内空气+高剂量ω-3 FA补充组。从怀孕第二天到出生,ω-3 FA以二十二碳六烯酸(DHA)和二十碳五烯酸(EPA)的混合物形式补充。高氧组的幼鼠从出生到出生后第5天(P5)暴露于80%的氧气中。在P5时,所有动物均被处死。通过细胞计数、TUNEL和活性半胱天冬酶-3免疫组织化学评估神经元细胞死亡和凋亡。组织病理学检查显示,母体ω-3 FA缺乏饮食和出生后高氧暴露与所选脑区神经元数量显著减少和凋亡细胞死亡显著增加有关。ω-3 FA治疗以剂量依赖方式显著减少了所选脑区的凋亡。我们的结果表明,母体ω-3 FA供应可能保护发育中的大脑免受高氧损伤。

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