Involvement of redox mechanisms in ischemic neuronal death

氧化还原机制参与缺血性神经元死亡

• 批准号: 10470291
• 负责人: HASHIMOTO Nobuo
• 金额: $ 7.55万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B).
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-10470291/
• 关键词: Cerebral ischemia; Redox; Thioredoxin; Cerebral infection; neuron; Cerebral ischemia; redox; Thioredoxin; cerebral infarction; redox regulation; oxidative stress; cerebral ischemia; thioredoxin; rat; mouse; ラット; ジャービル

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.

我们在啮齿类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。大鼠脑缺血（大脑中动脉短暂闭塞）和线粒体损伤（全身给药3-硝基丙酸）使大鼠脑神经元中硫氧还蛋白（TRX）及其mRNA表达上调，TRX过表达的突变小鼠对缺血损伤和兴奋毒性神经元损伤的抵抗能力较野生小鼠显著。缺血损伤发生3小时后全身给予TRX可显著减少小鼠脑梗死体积。在新生儿大鼠缺氧缺血模型（单侧颈总动脉闭塞+8%缺氧2小时）中，大脑皮层和海马中检测到强烈的TRX。提示TRX在多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。

项目成果

Takagi Y: "Expression and distribution of redox regulating protein, thioredoxin during transient focal brain ischemia in the rat."Neurosic Lett. 251. 25-28 (1998)

Takagi Y：“大鼠短暂局灶性脑缺血期间氧化还原调节蛋白硫氧还蛋白的表达和分布。”Neurosic Lett。

Sugino T et al: "3 Nitropropionic acid induces is chemic to lereace in gerbil hippocampus in vivo" Neuroscience Letters. 259. 9-12 (1999)

Sugino T 等人：“3 硝基丙酸在沙鼠海马体内诱导产生化学反应”《神经科学快报》。

Takagi Y: "Overexpression of thioredoxin in transgenic mice attenuates focal ischemic brain damage."Proc Natl Acad Sci (USA). 96. 4131-4136 (1999)

Takagi Y：“转基因小鼠中硫氧还蛋白的过度表达可减轻局灶性缺血性脑损伤。”Proc Natl Acad Sci（美国）。

Sugino,T: "Expression and distribution of redox regulatory protein, thioredoxin after metabolic impairment by 3-nitropropionic acid in rat brain"Neurosci Lett. 275. 145-148 (1999)

Sugino，T：“大鼠脑中 3-硝基丙酸代谢损伤后氧化还原调节蛋白、硫氧还蛋白的表达和分布”Neurosci Lett。

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