Molecular mechanisms of the membrane disorder in the senile dementia due to free radical

自由基导致老年痴呆膜紊乱的分子机制

• 批准号: 09670438
• 负责人: ADACHI Junko
• 金额: $ 2.05万
• 依托单位: kobe 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-09670438/
• 关键词: senile dementia; active oxygen; lipid peroxide; chemiluminescent detection; liquid chromatography-mass spectrometry

Senile dementia of cerebrovascular type is caused by ischemic injury of brain due to free radical-related lipid peroxide. First of all we investigated the methods for identification and quantification of cholesterol hydroperoxide. Next, we collected brain tissue of dementia and healthy subjects at autopsy. Then we divided into six regions, frontal cortex and white matter, parietotemporal cortex and white matter, and occipital cortex and white matter. Each tissue was homogenized and lipid was extracted. We identified 7-hydroperoxycholestero l 7-hydroxycholesterol, 7-ketocholesterol, and 5,6-epoxycholesterol by high performance liquid chromatography-mass spectrometory. In addtion we quantified 7 alpha -and 7- beta hydroperoxycholesterol by high performance liquid chromatography with chemiluminescent detection. We found an accumulation of 7-hydroperoxycholesterol in the brain of senile dementia. The accumulation was evident in parietotemporal white matter among the brain regions.

脑血管型老年性痴呆是由于自由基相关的脂质过氧化物导致脑部缺血性损伤所致。首先，我们研究了氢过氧化胆固醇的鉴定和定量方法。接下来，我们在尸检时收集了痴呆症患者和健康受试者的脑组织。然后我们分为六个区域，额叶皮层和白质，顶颞叶皮层和白质，枕叶皮层和白质。将每个组织匀浆并提取脂质。我们通过高效液相色谱-质谱法鉴定了 7-氢过氧胆固醇、7-羟基胆固醇、7-酮胆固醇和 5,6-环氧胆固醇。此外，我们通过高效液相色谱和化学发光检测对 7α-和 7-β 氢过氧胆固醇进行了定量。我们发现老年痴呆症患者的大脑中积聚了 7-氢过氧胆固醇。这种积累在大脑区域的顶颞叶白质中很明显。