Alteration in HIF-1 DNA binding activity following cerebral ischemia and its therapeutic application

由于iNOS在缺血脑组织中有表达，我们尝试用凝胶迁移率改变分析(EMSA)技术检测缺氧诱导因子(HIF)-1与缺氧反应增强子(HRE)的结合活性是否在缺血大鼠脑内增加。大脑中动脉短暂阻断2小时后，缺血核心及其周围区域(半暗带)的缺氧诱导因子(HIF)-1结合活性增加。缺血6小时后，甚至在对侧大脑半球也能检测到。在半影区，这种活动一直保持到24小时后，而在核心区消失。缺血后12~48h，缺血区血管壁和中性粒细胞表达iNOS，缺血中心能量衰竭和其他转录因子如iRF-1和NF-κB的参与可能解释了脑缺血后iNOS诱导和结合活性不同的原因。

Because iNOS is expressed in the ischemic brain, we tried to determine whether binding activity of hypoxia inducible factor (HIF) -1 to hypoxia-responsive enhancer (HRE) is increased in ischemic brain in the rat employing the electrophoretic mobility shift assay (EMSA) technique.One hour after 2-hour transient occlusion of the middle cerebral artery, hypoxia inducible factor (HIF) -1 binding activity was increased in the ischemic core and its surrounding area (penumbra). Six hours after ischemia, it was detected even in the contralateral hemisphere. In the penumbra, the activity was remained until 24 hours later, while it disappeared in the core. iNOS was induced during 12-48 hours after ischemia in the vessel walls and polymorphonuclear leukocytes within the ischemic territory.Energy failure in the ischemic core and involvement of the other transcription factors such as IRF-1 and NFκB might explain the discrepancy between HIF-1 binding activity and iNOS induction after cerebral ischemia.