Molecular analysis for ischemic tolerance of neuron

神经元缺血耐受的分子分析

• 批准号: 09671422
• 负责人: NOZAKI Kazuhiko
• 金额: $ 2.18万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09671422/
• 关键词: Ischemic tolerance; neuron; molecular biology; rat; gerbil; mouse; Ischemic to lerance; cerebral ischemia; rat; gerbil

The mechanisms of neuronal death and survival in ischemic brain are one of major topics in neuroscience. Recent papers have stressed the important role of mitochondria in ischemic neuronal damage in that both necrosis and apoptosis are induced by the dysfunction of mitochondria. On the other hand, the induction of ischemic tolerance in neuron after ischemic stress has been reported, but the molecular mechanisms of ischemic tolerance have not been elucidated. In the present study, we used several cerebral ischemic models including a. transient forebrain ischemia in gerbil, b. 3-nitropropionic acid-induced striatal damage in rat, c. permanent middle cerebral artery occlusion in rat, d. transient middle cerebral artery occlusion in rat, e. permanent middle cerebral artery occlusion in mouse in order to examine the relation of mitochondrial function and apoptosis and the mechanism of ischemic tolerance. We have demonstrated that apoptosis was involved in neuronal death in model a and b, that apoptosis related genes and poly(ADP-ribosyl)ation was involved in neuronal damage in model b and c, that thioredoxin is markedly induced in neuron in ischemic penumbra in model c and d, and that chemical preconditioning with 3-nitropropionic acid and overexpression of thioredoxin can induce ischemic tolerance in model a and e.

脑缺血后神经元死亡和存活的机制是神经科学研究的热点之一。最近的研究强调了线粒体在缺血性神经元损伤中的重要作用，即线粒体功能障碍导致神经元坏死和凋亡。另一方面，缺血应激诱导神经元缺血耐受的研究已有报道，但其分子机制尚未阐明。在本研究中，我们使用了几种脑缺血模型，包括a。沙鼠中的短暂前脑缺血，B. 3-硝基丙酸诱导的大鼠纹状体损伤，c.永久性大脑中动脉闭塞大鼠，d.短暂性大脑中动脉闭塞大鼠，目的：研究线粒体功能与细胞凋亡的关系及缺血耐受的机制。模型a和B中神经元死亡与凋亡有关，模型B和c中神经元损伤与凋亡相关基因和聚腺苷二磷酸核糖化有关，模型c和d中缺血半暗带神经元硫氧还蛋白明显诱导，模型a和e中3-硝基丙酸化学预处理和硫氧还蛋白过表达可诱导缺血耐受。

项目成果

Takagi Y et al: "Kedox control of reurenal damape during biain ischemia after middle cerebral artery occlusion in the rat" J Cereb Blood Flow & Metal. 18. 206-214 (1998)

Takagi Y 等人：“大鼠大脑中动脉闭塞后局部缺血期间 Kedox 对肾肾损伤的控制”J Cereb Blood Flow

Tokime, T.et al.: "Enhanced poly(ADP-ribosyl)ation after focal ischemia in rat rain" J Cereb Blood Flow Metab. 18. 991-997 (1998)

Tokime, T.et al.：“大鼠雨中局灶性缺血后增强的聚（ADP-核糖基）化”J Cereb Blood Flow Metab。

Takagi, Y.et al: "Redox Control of neuronal damage during brain ischemia after middle cerebral artery occlusion in the rat" J Cereb Blood Flow Metab. 18. 206-214 (1998)

Takagi, Y.et al：“大鼠大脑中动脉闭塞后脑缺血期间神经元损伤的氧化还原控制”J Cereb Blood Flow Metab。

Takagi Y,Tokime T,Nozaki K,Gon Y,Kikuchi H,Yodoi J: "Redox control of neuronal damage during brain ischemia after middle cerebral artery occlusion in the rat : Immunohistochemical and hybridization studies of thioredoxin." J Cereb Blood Flow Metab. 18. 20

Takagi Y、Tokime T、Nozaki K、Gon Y、Kikuchi H、Yodoi J：“大鼠大脑中动脉闭塞后脑缺血期间神经元损伤的氧化还原控制：硫氧还蛋白的免疫组织化学和杂交研究。”

Takagi Y et al: "Overexpression of thioredoxin in transgenic mice attenuates focal ischemic brain damage" Proc Natl Acad Sci (USA). (in press).

Takagi Y 等人：“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）。