卒中基因
缺血性意外发生后有短暂性性缺血性保护作用—此现象为缺血性耐受作用。对于缺血性耐受的分子生物学基础目前还了解甚少。明确涉及此过程的基因有助于促进细胞存活和卒中治疗。我们制作出了卒中前期、卒中期的鼠类模型，测定基因表达，以明确参与神经保护路径的基因。在鼠模型闭塞大脑中动脉(MCAO)15 min(卒中前期)、60 min(卒中期)或15 min，72 h后夹闭60 min(卒中前期+卒中期)。
提取卒中前期脑保护皮质区域的RNA，与寡核苷酸杂交。我们发现卒中期、卒中前期、卒中前期+卒中期所引起的基因变化很少有重叠。卒中能诱发强有力的基因上调表达，而卒中前期(随后发生卒中)会导致明显的下调表达。卒中所引起的基因上调表达提示应激/炎症通道激活、增强代谢作用和离子通道功能。卒中前期状态试图减少涉及这些通道的基因。随后的体外研究提示，卒中前期状态能降低K通道电压阈值、增加出血时间。我们的结果提示，通过基因转录作用重新调整卒中前期将发生缺血性脑损伤的状态，能够抑制代谢通道和免疫反应，降低离子通道活性、减少凝血。这些改变与冬眠中血流降低、耗氧减少的变化类似。
, 百拇医药
Brief episodes of ischemia protect against subsequent damaging ischemic event-a phenomenon known as ischemic tolerance. Little is known about the molecular underpinnings responsible for ischemic tolerance. Identifying genes involved in this process could provide insight into cell survival and treatment of stroke. We developed a murine model of ischemic preconditioning and subsequent stroke and used gene expression profiling to identify genes that may be involved in neuroprotective pathways. Middle cerebral artery occlusions (MCAO) were performed in mice for 15 min. (preconditioning), 60 min. (stroke) or 15 min. followed 72 hr later with 60 min (preconditioning plus stroke). RNA from a region of cortex that is protected by ischemic preconditioning was hybridized to oligonucleotide microarrays (Affymetrix). We found that stroke, ischemic preconditioning, and ischemic preconditioning plus stroke all induced gene changes that showed very little overlap among conditions. Stroke induced robust up-regulation of gene expression while preconditioning followed by stroke resulted in a marked down-regulation. Those genes upregulated by stroke suggested activation of stress/inflammatory pathways and increased metabolism and ion channel function. Preconditioning tended to decrease genes involved in these pathways. Follow-up experiments show preconditioning decreased voltage-gated potassium currents in vitro and increased bleeding time. Our results suggest that preconditioning re-programs the response to ischemic injury via transcriptional changes that may suppress metabolic pathways and immune responses, reduce ion channel activity, and decrease blood coagulation. These changes resemble evolutionarily conserved responses to decreased blood flow and oxygen availability that occur during hibernation., http://www.100md.com(Mary Stenzel-Poore(美国))
提取卒中前期脑保护皮质区域的RNA，与寡核苷酸杂交。我们发现卒中期、卒中前期、卒中前期+卒中期所引起的基因变化很少有重叠。卒中能诱发强有力的基因上调表达，而卒中前期(随后发生卒中)会导致明显的下调表达。卒中所引起的基因上调表达提示应激/炎症通道激活、增强代谢作用和离子通道功能。卒中前期状态试图减少涉及这些通道的基因。随后的体外研究提示，卒中前期状态能降低K通道电压阈值、增加出血时间。我们的结果提示，通过基因转录作用重新调整卒中前期将发生缺血性脑损伤的状态，能够抑制代谢通道和免疫反应，降低离子通道活性、减少凝血。这些改变与冬眠中血流降低、耗氧减少的变化类似。
, 百拇医药
Brief episodes of ischemia protect against subsequent damaging ischemic event-a phenomenon known as ischemic tolerance. Little is known about the molecular underpinnings responsible for ischemic tolerance. Identifying genes involved in this process could provide insight into cell survival and treatment of stroke. We developed a murine model of ischemic preconditioning and subsequent stroke and used gene expression profiling to identify genes that may be involved in neuroprotective pathways. Middle cerebral artery occlusions (MCAO) were performed in mice for 15 min. (preconditioning), 60 min. (stroke) or 15 min. followed 72 hr later with 60 min (preconditioning plus stroke). RNA from a region of cortex that is protected by ischemic preconditioning was hybridized to oligonucleotide microarrays (Affymetrix). We found that stroke, ischemic preconditioning, and ischemic preconditioning plus stroke all induced gene changes that showed very little overlap among conditions. Stroke induced robust up-regulation of gene expression while preconditioning followed by stroke resulted in a marked down-regulation. Those genes upregulated by stroke suggested activation of stress/inflammatory pathways and increased metabolism and ion channel function. Preconditioning tended to decrease genes involved in these pathways. Follow-up experiments show preconditioning decreased voltage-gated potassium currents in vitro and increased bleeding time. Our results suggest that preconditioning re-programs the response to ischemic injury via transcriptional changes that may suppress metabolic pathways and immune responses, reduce ion channel activity, and decrease blood coagulation. These changes resemble evolutionarily conserved responses to decreased blood flow and oxygen availability that occur during hibernation., http://www.100md.com(Mary Stenzel-Poore(美国))