Solberg Rønnaug, Longini Mariangela, Proietti Fabrizio, Perrone Serafina, Felici Cosetta, Porta Alessio, Saugstad Ola Didrik, Buonocore Giuseppe
Department of Pediatric Research, University of Oslo, Oslo University Hospital Rikshospitalet, Oslo, Norway.
Neonatology. 2017;112(1):1-8. doi: 10.1159/000454982. Epub 2017 Feb 1.
Perinatal hypoxic-ischemic brain damage is a major cause of acute mortality and chronic neurological morbidity in infants and children. Oxidative stress due to free radical formation and the initiation of abnormal oxidative reactions appears to play a key role. Docosahexanoic acid (DHA), a main component of brain membrane phospholipids, may act as a neuroprotectant after hypoxia-ischemia by regulating multiple molecular pathways and gene expression.
The aims of this study were to test the hypothesis that DHA provides significant protection against lipoperoxidation damage in the cerebral cortex and hippocampus in a neonatal piglet model of severe hypoxia-reoxygenation.
Newborn piglets, Noroc (LYLD), were subjected to severe global hypoxia. One group was resuscitated with ambient air (21% group, n = 11) and another also received 5 mg/kg of DHA 4 h after the end of hypoxia (21% DHA group, n = 10). After 9.5 h, tissues from the prefrontal cortex and hippocampus were sampled and the levels of isoprostanes, neuroprostanes, neurofurans, and F2-dihomo-isoprostanes were determined by the liquid chromatography triple quadrupole mass spectrometry technique.
Lipid peroxidation biomarkers were significantly lower in both the cortex and hippocampus in the DHA-treated group compared with the untreated group.
The present study demonstrates that DHA administration after severe hypoxia in newborn piglets has an antioxidative effect in the brain, suggesting a protective potential of DHA if given after injuries to the brain.
围产期缺氧缺血性脑损伤是婴幼儿急性死亡和慢性神经功能障碍的主要原因。自由基形成导致的氧化应激以及异常氧化反应的启动似乎起着关键作用。二十二碳六烯酸(DHA)是脑细胞膜磷脂的主要成分,可能通过调节多种分子途径和基因表达在缺氧缺血后起到神经保护作用。
本研究旨在验证以下假设:在严重缺氧复氧新生仔猪模型中,DHA对大脑皮层和海马体的脂质过氧化损伤具有显著保护作用。
新生仔猪,诺罗克(LYLD),经历严重的全身性缺氧。一组用空气复苏(21%组,n = 11),另一组在缺氧结束后4小时还接受5 mg/kg的DHA(21% DHA组,n = 10)。9.5小时后,采集前额叶皮层和海马体组织,采用液相色谱三重四极杆质谱技术测定异前列腺素、神经前列腺素、神经呋喃和F2 - 二高异前列腺素的水平。
与未治疗组相比,DHA治疗组的皮层和海马体中脂质过氧化生物标志物均显著降低。
本研究表明,新生仔猪严重缺氧后给予DHA对大脑具有抗氧化作用,提示脑损伤后给予DHA具有保护潜力。