The hypoxia-inflammation link and potential drug targets.
The hypoxia-inflammation link and potential drug targets.
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DOI：
10.1097/aco.0b013e32834873fd
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发表时间：
2011-08
期刊：
影响因子：
--
通讯作者：
Eltzschig HK
中科院分区：
文献类型：
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作者：
Koeppen M;Eckle T;Eltzschig HK
缺氧是我们已知的最强的转录刺激之一。在大多数情况下，缺氧引起的基因表达变化是为了使组织适应氧气供应有限的条件。一个众所周知的例子是，高海拔地区的体育锻炼会导致促红细胞生成素的转录诱导，促红细胞生成素的功能是增加携氧能力和红细胞体积。对缺氧条件下诱导促红细胞生成素的转录途径的研究导致了转录因子缺氧诱导因子（hypoxia-inducible factor， HIF）的发现，该转录因子今天被认为是缺氧适应的关键转录因子。手术患者经常面临缺氧或缺血的不利影响，例如在急性肾损伤、心肌、肠或肝缺血、急性肺损伤或器官移植期间。在本综述中，我们讨论了对缺氧的转录适应机制，并提供证据支持靶向缺氧诱导炎症可以代表改善围手术期预后的新药理学策略的假设。目前，这些策略还处于实验阶段，但我们希望在未来十年内，这些目标中的一些可以转化为围手术期患者护理。
Hypoxia represents one of the strongest transcriptional stimuli known to us. In most cases, hypoxia-induced changes in gene expression are directed towards adapting tissues to conditions of limited oxygen availability. As a well-known example, physical exercise at high-altitude results in the transcriptional induction of erythropoietin that functions to increase oxygen carrying capacity and red cell volume. Studies of the transcriptional pathway responsible for the induction of erythropoietin during conditions of hypoxia led to the discovery of the transcription factor hypoxia-inducible factor (HIF) that is known today as the key transcription factor for hypoxia adaptation. Surgical patients are frequently at risk for experiencing detrimental effects of hypoxia or ischemia, for example in the context of acute kidney injury, myocardial, intestinal or hepatic ischemia, acute lung injury or during organ transplantation. In the present review we discuss mechanisms of transcriptional adaptation to hypoxia and provide evidence supporting the hypothesis that targeting hypoxia-induced inflammation can represent novel pharmacologic strategies to improve perioperative outcomes. Currently, such strategies are being explored at an experimental level, but we hope that some of these targets can be translated into perioperative patient care within the next decade.