Huun Marianne Ullestad, Garberg Håvard T, Escobar Javier, Chafer Consuelo, Vento Maximo, Holme Ingar M, Saugstad Ola Didrik, Solberg Rønnaug
Department of Pediatric Research, Institute of Surgical Research, Oslo University Hospital, Rikshospitalet, Oslo, Norway, Tel.: +47-23-07-27-90.
Department of Pediatric Research, Institute of Surgical Research, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
J Perinat Med. 2018 Feb 23;46(2):209-217. doi: 10.1515/jpm-2016-0334.
Lipid peroxidation mediated by reactive oxygen species is a major contributor to oxidative stress. Docosahexaenoic acid (DHA) has anti-oxidant and neuroprotective properties. Our objective was to assess how oxidative stress measured by lipid peroxidation was modified by DHA in a newborn piglet model of hypoxia-ischemia (HI).
Fifty-five piglets were randomized to (i) hypoxia, (ii) DHA, (iii) hypothermia, (iv) hypothermia+DHA or (v) sham. All groups but sham were subjected to hypoxia by breathing 8% O2. DHA was administered 210 min after end of hypoxia and the piglets were euthanized 9.5 h after end of hypoxia. Urine and blood were harvested at these two time points and analyzed for F4-neuroprostanes, F2-isoprostanes, neurofuranes and isofuranes using UPLC-MS/MS.
F4-neuroprostanes in urine were significantly reduced (P=0.006) in groups receiving DHA. Hypoxia (median, IQR 1652 nM, 610-4557) vs. DHA (440 nM, 367-738, P=0.016) and hypothermia (median, IQR 1338 nM, 744-3085) vs. hypothermia+DHA (356 nM, 264-1180, P=0.006). The isoprostane compound 8-iso-PGF2α was significantly lower (P=0.011) in the DHA group compared to the hypoxia group. No significant differences were found between the groups in blood.
DHA significantly reduces oxidative stress by measures of lipid peroxidation following HI in both normothermic and hypothermic piglets.
活性氧介导的脂质过氧化是氧化应激的主要促成因素。二十二碳六烯酸(DHA)具有抗氧化和神经保护特性。我们的目的是评估在新生仔猪缺氧缺血(HI)模型中,DHA如何改变通过脂质过氧化测量的氧化应激。
55只仔猪被随机分为(i)缺氧组、(ii)DHA组、(iii)低温组、(iv)低温+DHA组或(v)假手术组。除假手术组外,所有组均通过呼吸8%氧气进行缺氧处理。在缺氧结束后210分钟给予DHA,在缺氧结束后9.5小时对仔猪实施安乐死。在这两个时间点采集尿液和血液,使用超高效液相色谱-串联质谱法分析F4-神经前列腺素、F2-异前列腺素、神经呋喃和异呋喃。
接受DHA的组中,尿液中的F4-神经前列腺素显著降低(P=0.006)。缺氧组(中位数,四分位间距1652 nM,610-4557)与DHA组(440 nM,367-738,P=0.016),以及低温组(中位数,四分位间距1338 nM,744-3085)与低温+DHA组(356 nM,264-1180,P=0.006)。与缺氧组相比,DHA组中的异前列腺素化合物8-异前列腺素F2α显著降低(P=0.011)。各组血液中未发现显著差异。
在正常体温和低温仔猪中,DHA通过测量HI后的脂质过氧化显著降低氧化应激。