Roles of in vivo REDOX systems by using in vivo ESR and transgenic mice

使用体内 ESR 和转基因小鼠体内氧化还原系统的作用

• 批准号: 07457530
• 负责人: UTSUMI Hideo
• 金额: $ 4.86万
• 依托单位: KYUSHU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07457530/
• 关键词: Transgenic animals; Electron spin resonance; antioxidative enzymes; Superoxide dismutase; 遺伝子組換え動物; フリーラジカル; 電子スピン共鳴法; 抗酸化剤; 生体レドックス; 活性酸素; ESR; スーパーオキシド; 遺伝子組換え

Reactive oxygen species and free radicals have important roles in physiological phenomena and diseases. There are discrepancy in the roles of antioxidative enzymes or antioxidants between in vitro and in vivo experiments. It is, therefore, important to investigate in vivo free radical reactions, to clarify roles of in vivo redox enzymes.In this study, role of Cu/Zn SOD was investigated under several kinds of oxidative stress using electron spin resonance (ESR) technique and Cu/Zn-SOD transgenic mice. In vivo ESR technique is the unique detection method to measure in vivo free radical reactions non-invasively.In physiological condition, it was indicated using newly synthesized redox probe that redox balances in SOD-Transgenics was changed. Overexpression of Cu/Zn-SOD on free radical reactions caused by 2,4,6-trichlorophenol (TCP) was also investigated using Cu/Zn-SOD transgenic mice and in vivo ESR spectroscopy. TCP enhanced free radical reactions in upper abdomen and increased serum GOT in a dose dependent manner. These enhancements were suppressed both by antioxidant and by overexpression of Cu/Zn-SOD,suggesting the relation of free radicals with liver injury caused by TCP and the suppression effect of endogenous Cu/Zn-SOD.Results of this study indicates that combination of transgenic animals and in vivo ESR technique will be useful to clarify the role of redox enzymes in diseases.

活性氧和自由基在生理现象和疾病中具有重要作用。体外和体内实验之间的抗氧化酶或抗氧化剂的作用存在差异。因此，研究体内自由基反应，阐明体内氧化还原酶的作用具有重要意义。本研究利用电子自旋共振（ESR）技术研究了Cu/Zn SOD在几种氧化应激下的作用，并研究了Cu/Zn SOD在多种氧化应激下的作用。 Cu/Zn-SOD 转基因小鼠。体内ESR技术是一种独特的非侵入性测量体内自由基反应的检测方法。在生理条件下，使用新合成的氧化还原探针表明SOD-Transgenics中的氧化还原平衡发生了改变。还使用 Cu/Zn-SOD 转基因小鼠和体内 ESR 光谱研究了 Cu/Zn-SOD 过表达对 2,4,6-三氯苯酚 (TCP) 引起的自由基反应的影响。 TCP以剂量依赖性方式增强上腹部自由基反应并增加血清GOT。这些增强作用被抗氧化剂和 Cu/Zn-SOD 的过表达所抑制，这表明自由基与 TCP 引起的肝损伤以及内源性 Cu/Zn-SOD 的抑制作用有关。动物和体内 ESR 技术将有助于阐明氧化还原酶在疾病中的作用。

项目成果

H.Utsumi et al.: "n Vivo ESR Measurement of Free Radical Reactions in Living Mice" Biodence Mechanisms against Environmental Stress. (inpress).

H.Utsumi 等人：“活体小鼠自由基反应的体内 ESR 测量”针对环境压力的 Biodence 机制。

韓 眞伊,竹下啓蔵,内海英雄: "生息マウス肺内のラジカル反応の無侵襲測定" 磁気共鳴と医学. 8. 47-50 (1997)

Mayi Han、Keizo Takeshita、Hideo Utsumi：“活体小鼠肺部自由基反应的非侵入性测量”《磁共振与医学》8. 47-50 (1997)。

Tomokazu Yoshida, Hiroshi Otake, Yukihiro Aramaki, Toshifumi Hata, Seishi Tsuchiya, Akira Hamada, and Hideo Utsumi: "Free radicals from 1-palmitoyl-2-arachidonoyl phosphatidylcholine liposomes in Fe2+/ascorbic acid solution" Biol.Pharm.Bull.19(16). 779-78

Tomokazu Yoshida、Hiroshi Otake、Yukihiro Aramaki、Toshifumi Hata、Seishi Tsuchiya、Akira Hamada 和 Hideo Utsumi：“Fe2/抗坏血酸溶液中 1-棕榈酰-2-花生四烯酰磷脂酰胆碱脂质体中的自由基”Biol.Pharm.Bull.19(

Yamaguchi T.: "In vivo ESR Studies on Pharmacokinetics and Metabolism of Parenteral Lipid Emulsion in Living Mice" Pharmaceutical Research. 13. 729-733 (1996)

Yamaguchi T.：“活体小鼠肠外脂质乳剂药代动力学和代谢的体内 ESR 研究”药物研究。

韓 眞伊, 竹下 啓蔵, 内海 英雄: "生息マウス肺内のラジカル反応の無侵襲測定" 磁気共鳴と医学. 8. 47-50 (1997)

Mayi Han、Keizo Takeshita、Hideo Utsumi：“活体小鼠肺部自由基反应的非侵入性测量”《磁共振与医学》8. 47-50 (1997)。