低氧复氧影响新生动物眼睛的全基因组表达。

Hypoxia-reoxygenation affects whole-genome expression in the newborn eye.

机构信息

Department of Pediatric Research, Clinic of Women and Child Health, Oslo University Hospital, Rikshospitalet, University of Oslo, Oslo, Norway.

出版信息

Invest Ophthalmol Vis Sci. 2014 Mar 10;55(3):1393-401. doi: 10.1167/iovs.13-13159.

DOI:10.1167/iovs.13-13159

PMID:24458145

Abstract

PURPOSE

Resuscitation of newborns is one of the most frequent procedures in neonatal medicine. The use of supplementary oxygen during resuscitation of the asphyxiated newborn has been shown to be detrimental to vulnerable tissues. We wanted to assess transcriptional changes in ocular tissue after the acute use of oxygen in the delivery room in a hypoxia-reoxygenation model of the newborn mouse.

METHODS

C57BL/6 mice (n = 57), postnatal day 7, were randomized to receive either 120 minutes of hypoxia, at 8% O2, followed by 30 minutes of reoxygenation with 21, 40, 60, or 100% O2 or to normoxia followed by 30 minutes of 21% or 100% O2. Whole ocular homogenates were analyzed by Affymetrix 750k expression array, and RT-PCR was performed for validation. Bayesian analysis of variance for microarray data (BAMarray) was used to identify single significant genes, and Gene Set Enrichment Analysis (GSEA) was applied to reveal significant pathway systems.

RESULTS

In total, ∼ 92% of the gene expression changes were altered in response to reoxygenation with 60% or 100% O2 compared to expression at the lower percentages of 21% and 40%. After 100% O2 treatment, genes involved in inflammation (Ccl12), angiogenesis (Igfr1, Stat3), and metabolism (Hk2) were upregulated. Pathway analyses after hypoxia-reoxygenation revealed significant alterations of six pathways which included apoptosis, TGF-beta signaling, oxidative phosphorylation, voltage-gated calcium channel complex, mitochondrion, and regulation of RAS protein signal transduction.

CONCLUSIONS

Hypoxia-reoxygenation can induce immediate transcriptional responses in ocular tissue involving inflammation, angiogenesis, energy failure, and Ras signaling.

摘要

目的

新生儿复苏是新生儿医学中最常见的操作之一。有研究表明，在窒息新生儿复苏过程中使用补充氧气会对脆弱组织造成损害。我们希望评估在新生小鼠缺氧-再复氧模型中，在产房内急性使用氧气对眼部组织的转录变化。

方法

C57BL/6 小鼠（n = 57），出生后第 7 天，随机接受 120 分钟的低氧（8% O2），然后进行 30 分钟的复氧，分别用 21%、40%、60%或 100% O2复氧，或用常氧进行 30 分钟的 21%或 100% O2复氧。用 Affymetrix 750k 表达谱芯片分析整个眼部匀浆，并进行 RT-PCR 验证。用微阵列数据的贝叶斯方差分析（BAMarray）来识别单基因显著变化，并用基因集富集分析（GSEA）来揭示显著的通路系统。

结果

总共，约 92%的基因表达变化是对用 60%或 100% O2复氧的反应，与 21%和 40%较低的百分比相比。用 100% O2 处理后，参与炎症（Ccl12）、血管生成（Igfr1、Stat3）和代谢（Hk2）的基因上调。缺氧-复氧后的通路分析显示，包括凋亡、TGF-β信号、氧化磷酸化、电压门控钙通道复合物、线粒体和 Ras 蛋白信号转导调节在内的六个通路发生了显著变化。