Resuscitation with 100% O2 increases cerebral injury in hypoxemic piglets
Resuscitation with 100% O2 increases cerebral injury in hypoxemic piglets
复制标题
DOI：
10.1203/01.pdr.0000141988.89820.e3
复制
发表时间：
2004-11-01
影响因子：
3.6
通讯作者：
Saugstad, OD
中科院分区：
文献类型：
--
作者：
Munkeby, BH;Borke, WB;Saugstad, OD
围产期窒息是新生儿立即和延迟性脑损伤的主要原因。我们假设，与环境空气相比，100% O-2的复苏对脑组织有害。我们通过细胞外甘油、基质金属蛋白酶（MMP）表达水平和氧化应激，评估了经过全氧缺氧和随后用21%或100% O-2复苏的新生仔猪的脑损伤。细胞外甘油通过脑微透析取样。通过明胶酶谱法、宽基质降解能力和实时PCR分析脑组织中MMP水平。用氧自由基吸收能力法测定总内源性抗氧化能力。100% O-2复苏后细胞外甘油比21% O-2复苏后增加50%。终点时复苏仔猪的总MMP活性较基线提高了一倍（p = 0.018）， 21% O-2 （p = 0.003）和100% O-2 （p = 0.001）复苏仔猪的MMP-2活性较基线显著提高。与21% O-2相比，100% O-2复苏组仔猪MMP-2 mRNA水平提高了100% （P < 0.05）。与基线（p 0.001）和21% O-2复苏仔猪相比，100% O-2复苏仔猪的氧自由基吸收能力值显著降低（p = 0.001）。总之，我们的数据显示MMP-2在基因和蛋白质水平上的活性增加，并伴有脑内甘油泄漏，可能是由氧化应激增强引起的。我们的研究结果表明，与21%的O-2复苏相比，100% O-2复苏对窒息仔猪的脑损伤更大。
Perinatal asphyxia is a major cause of immediate and postponed brain injury in the newborn. We hypothesized that resuscitation with 100% O-2 compared with ambient air is detrimental to the cerebral tissue. We assessed cerebral injury in newborn piglets that underwent global hypoxia and subsequent resuscitation with 21 or 100% O-2 by extracellular glycerol, matrix metalloproteinase (MMP) expression levels, and oxidative stress. Extracellular glycerol was sampled by cerebral microdialysis. MMP levels were analyzed in cerebral tissue by gelatin zymography, broad matrix degrading capacity, and real-time PCR. Total endogenous antioxidant capacity was measured by the oxygen radical absorbance capacity assay. Extracellular glycerol increased 50% after resuscitation with 100% O-2 compared with 21% O-2. Total MMP activity was doubled in resuscitated animals at endpoint compared with baseline (p = 0.018), and the MMP-2 activity was significantly increased in piglets that were resuscitated with 21% O-2 (P = 0.003) and 100% O-2 (P = 0.001) compared with baseline. MMP-2 mRNA level was 100% increased in piglets that were resuscitated with 100% O-2 as compared with 21% O-2 (P < 0.05). Oxygen radical absorbance capacity values in piglets that were resuscitated with 100% O-2 were considerably reduced compared with both baseline (p 0.001) and piglets that were resuscitated with 21% O-2 (p = 0.001). In conclusion, our data show increased MMP-2 activity at both gene and protein levels, accompanied with cerebral leakage of glycerol, presumably triggered by augmented oxidative stress. Our findings suggest that resuscitation of asphyxiated piglets with 100% O-2 is detrimental to the piglet brain compared with resuscitation with 21% O-2.