Studies on the behavior of free radicals as a neurotoxin in the central nervous system

自由基作为神经毒素在中枢神经系统中行为的研究

• 批准号: 03454292
• 负责人: TSUCHIHASHI Nobuaki
• 金额: $ 3.65万
• 依托单位: Fukushima Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-03454292/
• 关键词: In vivo ESR; Nitroxide; Aging; Idebenon; Vitamin E; Active oxgens; Antioxidant; Micloelectrode; 電子スピン共鳴; スーパーオキシドディスムターゼ; 酵素電極; ス-パオキシドディスムタ-ゼ

Free radicals have toxic effects to the central nervous system. To assess this effects, we studied the behavior of free radicals in the living biological system using novel methods.(1)in vivo ESR studyMetabolism of a stable nitroxide radical, TEMPOL, in living rats was observed using an L-band ESR system. TEMPOL was repeatedly injected at a 5-min interval via tail vein. The metabolism was analyzed in terms of the half-lives of TEMPOL elimination from the rat. In control animals, repeated injection of TEMPOL caused gradual prolongation of the half-lives. On the ontrary for rats receiving oral idebenone (a therapeutic agent for cerebro-vascular diseases) or vitamin E for 2-4 weeks, the prolongation was not found.In addition, analysis of the half-lives of TEMPOL in rats ranging from 4 to 16 weeks-old suggests a lower ability to eliminate radicals in older rats.(2)developments of microelectrode for bioradicalsNitric oxide(NO) is a important bioreguratory molecules. And it is assumed that NO also have toxic effects in the central nervous systems. The technology, however, is not available for direct analysis of the release and/or distributions of NO.We developed a microelectrode based on polymeric metalloporphyrin and carbon fibers. Using this electrode we have detected NO occuring in the rat brain by administratrion of NMDA.

自由基对中枢神经系统有毒性作用。为了评估这种影响，我们使用新方法研究了活体生物系统中自由基的行为。(1)体内ESR研究使用L波段ESR系统观察了活体大鼠中稳定的硝基氧自由基TEMPOL的代谢。通过尾静脉以5分钟间隔重复注射TEMPOL。根据大鼠体内 TEMPOL 消除的半衰期来分析代谢。在对照动物中，重复注射 TEMPOL 导致半衰期逐渐延长。相反，口服艾地苯醌（一种脑血管疾病治疗剂）或维生素E 2-4周的大鼠，未发现延长作用。此外，对4-16周龄大鼠体内TEMPOL的半衰期进行分析，发现老年大鼠清除自由基的能力较低。（2）生物自由基微电极的研究进展 氧化物（NO）是一种重要的生物调节分子。据推测，NO 对中枢神经系统也有毒性作用。然而，该技术无法直接分析 NO 的释放和/或分布。我们开发了一种基于聚合金属卟啉和碳纤维的微电极。使用该电极，我们通过施用 NMDA 检测到大鼠大脑中出现的 NO。

项目成果

Ogata, T.: "Developments of in vivo detection and imaging of free radicals by L-band electron spin resonance" Radiological Science. 34. 2-6 (1991)

Ogata, T.：“通过 L 波段电子自旋共振进行自由基体内检测和成像的进展”放射科学。

土橋 宣昭,石田 信一: "臨床医のための医用画像診断:ESR" 臨床画像. 7. 70-80 (1991)

Nobuaki Dobashi、Shinichi Ishida：“临床医生的医学图像诊断：ESR”《临床影像》7. 70-80 (1991)。

土橋 宣昭(分担執筆): "バイオサイエンスESR" 廣川書店, (1992)

土桥信明（撰稿人）：《Bioscience ESR》广川书店，（1992）

M.Ono: "A Surface-coil type resonator for in vivo ESR measurement" J.Magn.Reson.,Ser.B. (印刷中). (1994)

M.Ono：“用于体内 ESR 测量的表面线圈型谐振器”J.Magn.Reson.，Ser.B（出版中）。

Matsumoto, S.: "L-band ESR imaging of the dsitribution of the nitroxide radical aministered into a mouse or a rat." Jikikyoumei to Igaku. 2. 57-62 (1991)

Matsumoto, S.：“对小鼠或大鼠施用硝基氧自由基分布的 L 波段 ESR 成像。”