Wollen Embjørg J, Sejersted Yngve, Wright Marianne S, Madetko-Talowska Anna, Bik-Multanowski Miroslaw, Kwinta Przemko, Günther Clara-Cecilie, Nygård Ståle, Løberg Else Marit, Ystgaard Martin B, Pietrzyk Jacek J, Saugstad Ola D
Department of Pediatric Research, Clinic of Women and Child Health, Oslo University Hospital, Rikshospitalet, University of Oslo, Oslo, Norway.
1] Department of Pediatric Research, Clinic of Women and Child Health, Oslo University Hospital, Rikshospitalet, University of Oslo, Oslo, Norway [2] Department of Microbiology and CMBN, University of Oslo, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
Pediatr Res. 2014 Apr;75(4):517-26. doi: 10.1038/pr.2013.249. Epub 2013 Dec 27.
Supplemental oxygen used during resuscitation can be detrimental to the newborn brain. The aim was to determine how different oxygen therapies affect gene transcription in a hypoxia-reoxygenation model.
C57BL/6 mice (n = 56), postnatal day 7, were randomized either to 120 min of hypoxia 8% O2 followed by 30 min of reoxygenation with 21, 40, 60, or 100% O2, or to normoxia followed by 30 min of 21 or 100% O2. Affymetrix 750k expression array was applied with RT-PCR used for validation. Histopathology and immunohistochemistry 3 d after hypoxia-reoxygenation compared groups reoxygenated with 21 or 100% O2 with normoxic controls (n = 22).
In total, ~81% of the gene expression changes were altered in response to reoxygenation with 60 or 100% O2 and constituted many inflammatory-responsive genes (i.e., C5ar2, Stat3, and Ccl12). Oxidative phosphorylation was downregulated after 60 or 100% O2. Iba1(+) cells were significantly increased in the striatum and hippocampal CA1 after both 21 and 100% O2.
In the present model, hypoxia-reoxygenation induces microglial accumulation in subregions of the brain. The transcriptional changes dominating after applying hyperoxic reoxygenation regimes include upregulating genes related to inflammatory responses and suppressing the oxidative phosphorylation pathway.
复苏过程中使用的补充氧气可能对新生儿大脑有害。目的是确定不同的氧气疗法如何影响缺氧-复氧模型中的基因转录。
将出生7天的C57BL/6小鼠（n = 56）随机分为两组，一组接受8%氧气的缺氧处理120分钟，然后分别用21%、40%、60%或100%的氧气进行30分钟的复氧；另一组接受常氧处理，然后用21%或100%的氧气进行30分钟处理。应用Affymetrix 750k表达阵列，并使用RT-PCR进行验证。在缺氧-复氧3天后，对用21%或100%氧气复氧的组与常氧对照组（n = 22）进行组织病理学和免疫组织化学分析。
总的来说，约81%的基因表达变化是对60%或100%氧气复氧的反应而改变的，其中包括许多炎症反应基因（即C5ar2、Stat3和Ccl12）。60%或100%氧气复氧后氧化磷酸化下调。21%和100%氧气复氧后，纹状体和海马CA1区的Iba1(+)细胞均显著增加。
在本模型中，缺氧-复氧诱导大脑亚区域的小胶质细胞积聚。高氧复氧方案后占主导地位的转录变化包括上调与炎症反应相关的基因和抑制氧化磷酸化途径。
