Division of Newborn Medicine, Department of Pediatrics, Floating Hospital for Children at Tufts Medical Center, Boston, MA 02111, USA.
Free Radic Biol Med. 2010 Sep 15;49(6):992-6. doi: 10.1016/j.freeradbiomed.2010.05.026. Epub 2010 Jun 8.
Neonates are exposed to elevated levels of reactive oxygen species as they transition from a hypoxic intrauterine to a normoxic extrauterine environment at birth. This increased oxidative stress is associated with neonatal morbidity. Current antioxidant supplementation treatment strategies have yet to translate into improved neonatal outcomes. Our understanding of a newborn's intricate redox balance, particularly at the genomic level, remains limited. Here, we performed genomic microarray analyses (approximately 14,500 genes) on extracted mRNA from umbilical cord whole blood at term gestation (n=10). Bioinformatic analyses identified 282 genes (2.0%) that were consistently present within the highest quintile of expressed genes. These genes were highly associated with oxidant stress and included superoxide dismutase 1, catalase, peroxiredoxins, and uncoupling proteins. Pathway analyses identified statistically significantly overrepresented functional pathways including "oxidative stress," "oxidative stress response mediated by nuclear factor-erythroid 2-related factor," "hypoxia-inducible factor signaling," and "mitochondrial dysfunction" (p<0.05). These results suggest that neonates require high levels of antioxidants and an intricate cellular redox balance to ensure a successful transition to the extrauterine environment. Understanding the genes necessary to maintain this delicate redox balance may lead to the development of alternative treatment strategies.
新生儿在从低氧的宫内环境过渡到正常氧的宫外环境时，会暴露在高水平的活性氧物质中。这种增加的氧化应激与新生儿发病率有关。目前的抗氧化补充治疗策略尚未转化为改善新生儿结局。我们对新生儿复杂的氧化还原平衡的理解，特别是在基因组水平上，仍然有限。在这里，我们对足月妊娠（n=10）脐带全血提取的 mRNA 进行了基因组微阵列分析（约 14500 个基因）。生物信息学分析确定了 282 个基因（2.0%），这些基因在表达最高的五分位数中始终存在。这些基因与氧化剂应激高度相关，包括超氧化物歧化酶 1、过氧化氢酶、过氧化物酶和解偶联蛋白。通路分析确定了具有统计学意义的代表性功能途径，包括“氧化应激”、“核因子-红细胞 2 相关因子介导的氧化应激反应”、“缺氧诱导因子信号”和“线粒体功能障碍”（p<0.05）。这些结果表明，新生儿需要高水平的抗氧化剂和复杂的细胞氧化还原平衡，以确保成功过渡到宫外环境。了解维持这种微妙的氧化还原平衡所需的基因可能会导致替代治疗策略的发展。
