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首页> 外文期刊>Scientific reports. >Transcription Factors Regulation in Human Peripheral White Blood Cells during Hypobaric Hypoxia Exposure: an in-vivo experimental study
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Transcription Factors Regulation in Human Peripheral White Blood Cells during Hypobaric Hypoxia Exposure: an in-vivo experimental study

机译：低收伤缺氧暴露过程中人外周血细胞的转录因子调控：体内实验研究

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High altitude is a natural laboratory, within which the clinical study of human physiological response to hypobaric hypoxia (HH) is possible. Failure in the response results in progressive hypoxemia, inflammation and increased tissue oxidative stress (OxS). Thus, investigating temporal changes in key transcription factors (TFs) HIF-1α, HIF-2α, NF-κB and NRF2 mRNA levels, relative to OxS and inflammatory markers, may reveal molecular targets which contrast deleterious effects of hypoxia. Biological samples and clinical data from 15 healthy participants were collected at baseline and after rapid, passive ascent to 3830?m (24?h and 72?h). Gene expression was assessed by qPCR and ROS generation was determined by EPR spectroscopy. Oxidative damage and cytokine levels were estimated by immuno or enzymatic methods. Hypoxia transiently enhanced HIF-1α mRNA levels over time reaching a peak after 24?h. Whereas, HIF-2α and NRF2 mRNA levels increased over time. In contrast, the NF-κB mRNA levels remained unchanged. Plasma levels of IL-1β and IL-6 also remained within normal ranges. ROS production rate and markers of OxS damage were significantly increased over time. The analysis of TF-gene expression suggests that HIF-1α is a lead TF during sub-acute HH exposure. The prolongation of the HH exposure led to a switch between HIF-1α and HIF-2α/NRF2, suggesting the activation of new pathways. These results provide new insights regarding the temporal regulation of TFs, inflammatory state, and ROS homeostasis involved in human hypoxic response, potentially also relevant to the mediation of diseases that induce a hypoxic state.
机译：高海拔是一种自然实验室，在那中，人体生理反应对低钙缺氧（HH）的临床研究是可能的。响应失败导致进行性低氧血症，炎症和增加组织氧化应激（牛）。因此，研究关键转录因子（TFS）HIF-1α，HIF-2α，NF-κB和NRF2 mRNA水平的时间变化相对于牛和炎症标志物，可能会揭示对比缺氧的有害影响的分子靶标。从基线和快速，被动上升到3830？m（24？h和72℃）的生物样本和临床资料。通过QPCR评估基因表达，通过EPR光谱法测定ROS生成。通过免疫或酶法估算氧化损伤和细胞因子水平。缺氧瞬时增强HIF-1αmRNA水平随时间达到24℃后的峰。然而，HIF-2α和NRF2 mRNA水平随着时间的推移而增加。相比之下，NF-κBmRNA水平保持不变。 IL-1β和IL-6的血浆水平仍然存在于正常范围内。随着时间的推移，ROS生产率和牛的标记显着增加。 TF-基因表达的分析表明，HIF-1α是亚急性HH暴露期间的引线TF。 HH暴露的延长导致HIF-1α和HIF-2α/ NRF2之间的开关，表明新途径的激活。这些结果提供了关于TFS，炎症状态和ROS宿主参与人类缺氧反应的时间调节的新见解，可能与诱导缺氧状态的疾病的调解也相关。

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