Involvement of redox mechanisms in ischemic neuronal death

我们在啮齿动物模型中研究了氧化还原机制在缺血性神经元损伤中的作用。脑缺血(线栓阻断大脑中动脉)和线粒体损伤(全身注射3-硝基丙酸)可上调大鼠脑神经元中硫氧还蛋白(TRX)及其mRNA的表达，高表达TRX的突变小鼠与野生型小鼠相比具有明显的抗缺血损伤和兴奋性毒性神经元损伤的能力。在小鼠脑缺血发作后立即全身性给予TRX 3小时，可显著减少小鼠脑梗塞体积。在新生大鼠缺氧缺血模型(单侧颈总动脉结扎+8%低氧2小时)中，Trx在大脑皮层和海马区呈强阳性表达。这些结果表明，Trx在各种啮齿动物脑缺血模型中发挥神经保护分子的作用，可能成为一种新的治疗人类缺血性神经元损伤的药物。

We investigated the role of redox mechanisms in ischemic neuronal damage in rodent models. Cerebral ischemia (transient occlusion of middle cerebral artery with thread) and mitochondrial impairment (by systemic administration of 3-nitropropionic acid) up-regulated thioredoxin (TRX) and its mRNA in neurons of rat brain, and mutant mice with overexpression of TRX showed significant resistance to ischemic insults and excitotoxic neuronal damages compared with wild ones. Systemic administration of TRX just after the onset of ischemic insult for 3 hours significantly reduced cerebral infarct volume in mice. In hypoxia-ischemia model of rat neonates (unilateral common carotid artery occlusion+8% hypoxia for 2 hours), TRX was strongly detected in cerebral cortex and hippocampus. These results imply that TRX acts as a neuroprotective molecule in various rodent cerebral ischemic models and may serve as a new therapeutic agent against ischemic neuronal damage in human.