Elevated free radical products in the cerebrospinal fluid of VLBW infants with cerebral white matter injury
Elevated free radical products in the cerebrospinal fluid of VLBW infants with cerebral white matter injury
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DOI：
10.1203/01.pdr.0000020088.11295.13
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发表时间：
2002-08-01
影响因子：
3.6
通讯作者：
Winterbourn, C
中科院分区：
文献类型：
--
作者：
Inder, T;Mocatta, T;Winterbourn, C
自由基介导的细胞损伤已被假设在早产儿白色物质损伤的发病机制中起关键作用，但缺乏直接证据。在1999年4月至2001年5月期间，22名极低出生体重儿、30名足月儿和17名成人采集了脑脊液（CSF）样本用于临床指征。仅分析了没有任何脑膜炎症证据的CSF样本的脂质过氧化产物、8-异前列腺素和丙二醛（MDA）以及作为蛋白质氧化指标的蛋白质羰基的水平。监测氯酪氨酸作为中性粒细胞氧化活性的量度。在足月时磁共振成像显示白色物质损伤的早产儿中，与健康早产儿、足月儿和成人对照组相比，CSF中蛋白质羰基水平显著升高（均p < 0.001）。有白色物质损伤的早产儿和成人对照组之间的脂质过氧化产物8-异前列烷和MDA水平存在显著差异（异前列烷p = 0.02，MDA p = 0.014）。与没有白色损伤的早产儿相比，有白色损伤的早产儿中8-异前列烷水平有升高的趋势（p = 0.08），14名白色损伤的早产儿中有5名的水平比成人范围的上限高10倍以上。任何组之间的氯酪氨酸水平均无显著差异。这些初步的数据提供了证据，在人类早产儿的白色物质损伤的演变过程中，氧化产物的升高。
Free radical mediated cellular injury has been hypothesized to play a key role in the pathogenesis of white matter injury in the premature infant, although direct evidence is lacking. Between April 1999 and May 2001, 22 very low birthweight infants, 30 term infants, and 17 adults had samples of cerebrospinal fluid (CSF) collected for clinical indications. Only CSF samples without any evidence of meningeal inflammation were analyzed for the levels of the lipid peroxidation products, 8-isoprostane and malondialdehyde, (MDA), and protein carbonyls as a measure of protein oxidation. Chlorotyrosine was monitored as a measure of neutrophil oxidative activity. In the premature infants with subsequent evidence of white matter injury on magnetic resonance imaging at term, there was a significant elevation in the CSF level of protein carbonyls in comparison with the level in healthy premature infants, term infants, and adult controls (all p < 0.001). A significant difference in the levels of the lipid peroxidation products, 8-isoprostane and MDA, was apparent between premature infants with white matter injury and adult controls (isoprostanes p = 0.02, MDA p = 0.014). There was a trend toward higher levels of 8-isoprostane in the premature infants with white matter injury in comparison with those without white matter injury (p = 0.08), with 5 of the 14 infants with white matter injury having levels that were more than 10-fold higher than the top of the adult range. There was no significant difference in the level of chlorotyrosines among any of the groups. These preliminary data provide evidence of an association of elevated oxidative products during the evolution of white matter injury in the human premature infant.