Hypoxic preconditioning protects against ischemic brain injury.
Hypoxic preconditioning protects against ischemic brain injury.
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DOI：
10.1007/bf03206565
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发表时间：
2004-01-01
期刊：
影响因子：
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通讯作者：
Bernaudin, Myriam
中科院分区：
文献类型：
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作者：
Sharp, Frank R;Ran, Ruiqiong;Bernaudin, Myriam
暴露于短暂中度缺氧（8%至10%氧气，3小时）的动物在1至2天后免受脑和心脏缺血。这种低氧预适应需要新的RNA和蛋白质合成。这种缺氧诱导的耐受性的机制与缺氧诱导因子（HIF）的诱导相关，缺氧诱导因子（HIF）是一种转录因子异二聚体复合物，由诱导型HIF-1 α和组成型HIF-1 β蛋白组成，与许多HIF靶基因中的缺氧反应元件结合。我们最近的研究表明HIF-1 α与新生大鼠脑缺氧耐受相关。HIF靶基因也是在低氧诱导的耐受之后诱导的，包括血管内皮生长因子、促红细胞生成素、葡萄糖转运蛋白、糖酵解酶和许多其他基因。这些基因中的一些或全部可能有助于低氧诱导的抗缺血保护。HIF对糖酵解酶的诱导部分解释了脑和其他组织中的巴斯德效应。低氧诱导的耐受性不太可能等同于用单一HIF靶基因蛋白的治疗，因为包括Egr-1（NGFI-A）在内的其他转录因子已涉及基因表达的低氧调节。了解缺氧耐受的机制和基因可能为治疗缺血性损伤和促进恢复提供新的治疗靶点。
Animals exposed to brief periods of moderate hypoxia (8% to 10% oxygen for 3 hours) are protected against cerebral and cardiac ischemia between 1 and 2 days later. This hypoxia preconditioning requires new RNA and protein synthesis. The mechanism of this hypoxia-induced tolerance correlates with the induction of the hypoxia-inducible factor (HIF), a transcription factor heterodimeric complex composed of inducible HIF-1alpha and constitutive HIF-1beta proteins that bind to the hypoxia response elements in a number of HIF target genes. Our recent studies show that HIF-1alpha correlates with hypoxia induced tolerance in neonatal rat brain. HIF target genes, also induced following hypoxia-induced tolerance, include vascular endothelial growth factor, erythropoietin, glucose transporters, glycolytic enzymes, and many other genes. Some or all of these genes may contribute to hypoxia-induced protection against ischemia. HIF induction of the glycolytic enzymes accounts in part for the Pasteur effect in brain and other tissues. Hypoxia-induced tolerance is not likely to be equivalent to treatment with a single HIF target gene protein since other transcription factors including Egr-1 (NGFI-A) have been implicated in hypoxia regulation of gene expression. Understanding the mechanisms and genes involved in hypoxic tolerance may provide new therapeutic targets to treat ischemic injury and enhance recovery.