Nien9C oxiok in vasospasm folloroing experimenibl subamchnoid hemo rrhege

Nien9C Oxiok 在蛛网膜下腔出血后血管痉挛实验中的应用

• 批准号: 07671495
• 负责人: TOMINAGA Teiji
• 金额: $ 1.34万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07671495/
• 关键词: subarachnoid hemorrhage; vasospasm; free radical; SOD; mouse; ラット; 一酸化窒素

The purpose of the present study is to examine whether superoxide dismutase (SOD) suppresses experimental vasospasm following subarachnoid hemorrhage (SAH) using transgenic mice overexpressing human Cu-Zu SOD.This transgenic mouse was produced by insertion of human CuZn-SOD gene to the MCH (IRC) mouse, and has three times of SOD activity compared with non-transgenic mouse. The experimental SAH was produced by perforation of the anterior cerebral artery with a nylon suture inserted from the internal carotid artery. The mice were perfused from the ascending aorta with 10% formalin solution followed by carbon gel solution 4 hours, 1 day, 3 days, 7 days, and 14 days after the SAH.The diameter of the proximal middle cerebral artery (MCA) was measured under phase-contrast microscope. The survival rate of the SOD-transgenic mice 3 days after SAH,approximately 70%, was not statistically different from that of non-transgenic mice. The MCA diameter of non-transgenic mice without SAH was 138.5(]SY.+-。[)14.5mum(control value, mean(]SY.+-。[)SD,n=12). The MCA diameter of non-transgenic mice did not change compared with the control values 4 hours, 1 day, 7 days, and 14 days after the SAH,and significantly decreased to 110.5(]SY.+-。[)20.5mum (n=16, p<0.01) only 3 days after the SAH.Three days after the SAH,the MCA diameter of the SOD-transgenic mice was larger than that of the non-transgenic mice with statistical significance (127.9(]SY.+-。[)20.2mum, n=20 ; p<0.05). These results suggest that CuZn-SOD can mitigate vasospasm caused by SAH and that the mechanism underlying vasospasm includes free radical reactions associated with superoxide anion.

本研究的目的是利用过表达人 Cu-Zu SOD 的转基因小鼠来检测超氧化物歧化酶 (SOD) 是否抑制蛛网膜下腔出血 (SAH) 后的实验性血管痉挛。这种转基因小鼠是通过将人 CuZn-SOD 基因插入到 MCH (IRC) 小鼠中而产生的，与非转基因小鼠相比，其 SOD 活性是非转基因小鼠的三倍。实验性 SAH 是通过从颈内动脉插入尼龙缝线对大脑前动脉进行穿孔而产生的。小鼠蛛网膜下腔出血后4小时、1天、3天、7天、14天从升主动脉灌注10%福尔马林溶液，然后灌注碳凝胶溶液。相差显微镜下测量近端大脑中动脉（MCA）直径。 SOD转基因小鼠SAH后3天的存活率约为70%，与非转基因小鼠无统计学差异。未发生SAH的非转基因小鼠的MCA直径为138.5(]SY.+-。[)14.5mum(对照值，平均值(]SY.+-。[)SD,n=12)。 SAH后4小时、1天、7天、14天，非转基因小鼠的MCA直径与对照值相比没有变化，SAH后仅3天，MCA直径显着下降至110.5(]SY.+-。[)20.5mum (n=16, p<0.01)。SAH后3天，SOD转基因小鼠的MCA直径大于对照组 非转基因小鼠具有统计学意义(127.9(]SY.+-。[)20.2mum, n=20 ; p<0.05)。这些结果表明CuZn-SOD可以减轻SAH引起的血管痉挛，并且血管痉挛的机制包括与超氧阴离子相关的自由基反应。

项目成果

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和田修：《内科治疗指南95》文科堂，1565（1995）

Tsuyoshi Ohnishi et al: "Central Nervous System Trama:Research Techniques" CRC Press, 560 (1995)

Tsuyoshi Ohnishi 等人：“中枢神经系统创伤：研究技术”CRC Press，560 (1995)