Munkeby Berit Holthe, Børke Wenche Bakken, Bjørnland Kristin, Sikkeland Liv Ingunn B, Borge Grethe Iren A, Lømo Jon, Rivera Santiago, Khrestchatisky Michel, Halvorsen Bente, Saugstad Ola Didrik
Department of Pediatric Research, Rikhospitalet University Hospital, Oslo, Norway.
Pediatr Res. 2005 Sep;58(3):542-8. doi: 10.1203/01.PDR.0000179407.46810.2D.
We hypothesized that resuscitation with 100% O2 compared with 21% O2 is detrimental to pulmonary tissue. The pulmonary injury was assessed by matrix metalloproteinase (MMP) activity, oxidative stress, IL-8, and histology 2.5 h after resuscitation from a hypoxic state. In pulmonary tissue extracts, MMP activity was analyzed by broad matrix-degrading capacity (total MMP) and zymography. MMP-2 mRNA expression was evaluated by quantitative real-time PCR. Total endogenous antioxidant capacity was measured by the oxygen radical absorbance capacity (ORAC) assay, and IL-8 was analyzed by ELISA technique. In bronchoalveolar lavage (BAL) fluid, MMPs were analyzed by zymography. In pulmonary tissue, pro- and active MMP-2 levels were increased in piglets that were resuscitated with 100% O2 compared with 21% O2. Pro-MMP-9, total MMP activity, and MMP-2 mRNA levels were significantly increased in resuscitated piglets compared with baseline. Net gelatinolytic activity increased in submucosa and blood vessels after 100% O2 and only in the blood vessels after 21% O2. Compared with baseline, ORAC values were considerably lowered in the resuscitated piglets and significantly reduced in the 100% O2 versus 21% O2 group. In BAL fluid, both pro-MMP-9 and pro-MMP-2 increased 2-fold in the 100% O2 group compared with 21% O2. Moreover, IL-8 concentration increased significantly in piglets that were resuscitated with 100% O2 compared with 21% O2, suggesting a marked proinflammatory response in the pulmonary tissue. Altogether, these data strongly suggest that caution must be taken when applying pure O2 to the newborn infant.
我们假设，与使用21%氧气进行复苏相比，使用100%氧气进行复苏对肺组织有害。在从低氧状态复苏2.5小时后，通过基质金属蛋白酶（MMP）活性、氧化应激、白细胞介素-8（IL-8）和组织学评估肺损伤。在肺组织提取物中，通过广泛的基质降解能力（总MMP）和酶谱分析来分析MMP活性。通过定量实时聚合酶链反应（PCR）评估MMP-2信使核糖核酸（mRNA）表达。通过氧自由基吸收能力（ORAC）测定法测量总内源性抗氧化能力，并通过酶联免疫吸附测定（ELISA）技术分析IL-8。在支气管肺泡灌洗（BAL）液中，通过酶谱分析MMP。在肺组织中，与使用21%氧气复苏的仔猪相比，使用100%氧气复苏的仔猪中前MMP-2和活性MMP-2水平升高。与基线相比，复苏仔猪中的前MMP-9、总MMP活性和MMP-2 mRNA水平显著升高。100%氧气复苏后，黏膜下层和血管中的净明胶酶解活性增加，而21%氧气复苏后仅血管中增加。与基线相比，复苏仔猪中的ORAC值大幅降低，100%氧气组与21%氧气组相比显著降低。在BAL液中，与21%氧气组相比，100%氧气组中的前MMP-9和前MMP-2均增加了2倍。此外，与21%氧气复苏的仔猪相比，100%氧气复苏的仔猪中IL-8浓度显著增加，表明肺组织中存在明显的促炎反应。总之，这些数据强烈表明，对新生儿应用纯氧时必须谨慎。
