Taie Satoshi, Ono Junichiro, Iwanaga Yasuyuki, Tomita Shuhei, Asaga Takehiko, Chujo Kosuke, Ueki Masaaki
Department of Anesthesiology and Emergency Medicine, Kagawa University, Ikenobe, Miki-cho, Kagawa, Japan.
J Clin Neurosci. 2009 Aug;16(8):1056-60. doi: 10.1016/j.jocn.2008.09.024. Epub 2009 May 17.
Sublethal hypoxia induces tolerance to subsequent hypoxic insults in a process known as hypoxic preconditioning (HP). Hypoxia-inducible factor-1 alpha (HIF-1 alpha) is a key transcription protein involved in the mechanism of HP. In this study, we investigated the effects of HP on tissue oxygenation and expression of HIF-1 alpha gene targets in the brain using neural cell-specific HIF-1 alpha-deficient mice. The animals were exposed to 8% oxygen for 3 hours. Twenty-four hours later, the oxygen partial pressure (pO(2)) of brain tissue and gene expression were measured during hypoxia. HP improved the pO(2) of brain tissue during subsequent hypoxia with upregulated inducible nitric oxide synthase in wild-type mice, whereas HP had no detectable effect in the mutant mice. Our results indicate that the protective effects of HP may be partially mediated by improving tissue oxygenation via HIF-1 alpha and inducible nitric oxide synthase.
亚致死性缺氧在一个被称为缺氧预处理（HP）的过程中诱导对随后缺氧损伤的耐受性。缺氧诱导因子-1α（HIF-1α）是参与HP机制的关键转录蛋白。在本研究中，我们使用神经细胞特异性HIF-1α缺陷小鼠研究了HP对脑组织氧合及HIF-1α基因靶点表达的影响。将动物暴露于8%氧气环境中3小时。24小时后，在缺氧期间测量脑组织的氧分压（pO₂）和基因表达。HP改善了野生型小鼠随后缺氧期间脑组织的pO₂，同时诱导型一氧化氮合酶上调，而HP在突变小鼠中未产生可检测到的影响。我们的结果表明，HP的保护作用可能部分是通过HIF-1α和诱导型一氧化氮合酶改善组织氧合来介导的。
