PROTECTION BY ANTOXIDANTS OF ISCHEMIC CELLULAR DAMAGE

抗氧化剂对缺血性细胞损伤的保护

• 批准号: 61570139
• 负责人: KAWASAKI Takashi
• 金额: $ 1.28万
• 依托单位: HIROSHIMA UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1986
• 资助国家: 日本
• 起止时间: 1986 至 1987
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-61570139/
• 关键词: Ischemic cellular damage; Antioxidants; Protection of ischemic organ damage; Endotoxin shock; 虚血肝移植保護; 虚血細胞障害; 還元型グルタチオン; 抗酸化作用; ATP再合成促進; 障害保護作用

Liver ischemia-reperfusion induced cellular damage caused by stimulated lipid peroxidation on biomembranes, especialy after reperfusion, which resulted in a marked decrease in ATP resynthesis after reperfusion due to mitochondrial dysfunction, and a decrease in the survival rate depending on ischemic periods. The administration of either coenzyme q_<10> (CoQ_<10>) or <alpha>-tocopherol (<alpha>-Toc) prior to ischemia completely suppressed the stimulated lipid peroxidation, and raised ATP resynthesis due to reversal of the mitochondrial dysfunction, which were accompained by a marked rise in the survival rate from 0% to 60% after 90-min ischemia. When endogenous levels of CoQ_<10> homologs (CoQ_9, CoQ_<10>), <alpha>-Toc and reduced glutathione (GSH) in the liver were determined during 90-min ischemia and following 60-min reperfusion period, the lwvels of <alpha>-Toc and GSH decreased during ischemia, which were not protected by CoQ_<10> pretreatment. The levels of endogenous antioxidant … More s tested decreased markedly after reperfution following to ischemia, which were completely reversed by the administration of either CoQ_<10> or <alpha>-Toc. These results obtained are compatible with the assumption that cellular damage caused by hepatic ischemia-reperfusion can be explained by free radical injury, and that antioxidants administered can protect cellular damage from lipid peroxidation by either radical scavenging and antioxidant actions.The protective effect of CoQ_<10> on ischemic damage could be demonstrated with orthotopic transplantation of the rat liver subjected to warm ischemia for 30 min: the survival rate of recipient rats increased from 0% to 45% in CoQ_<10>-pretreated group.Cellular damage due to endotoxemia was also explained, at least in part, by stimulated lipid peroidation. The administration of CoQ_<10> and <alpha>-Toc completely suppressed lipid peroxidation with a marked improvement of energy metabolism as well as endogenous levels of antioxidants, which, resulted in a marked rise of the survival rate. Less

肝缺血再灌注后，尤其是再灌注后，由于细胞膜脂质过氧化反应的刺激，导致细胞ATP合成减少，存活率随缺血时间的延长而降低。缺血前给予辅酶q_<10>（CoQ_<10>）或α<alpha>-生育酚（<alpha>-Toc）可完全抑制脂质过氧化反应，逆转线粒体功能障碍，使ATP再合成增加，并使缺血90分钟后的存活率从0%显著提高到60%。测定<10><10><alpha>肝脏缺血90分钟和再灌注60分钟时内源性辅酶Q_9、辅酶Q_4、-Toc和还原型谷胱甘肽（GSH）的含量，发现<alpha>缺血时-Toc和GSH的含量降低，而辅酶Q_4预处理对这些活性无保护作用<10>。内源性抗氧化剂水平 ...更多信息 缺血再灌注后，s值明显降低，而CoQ_<10>2或<alpha>-Toc可完全逆转此现象。这些结果与肝缺血再灌注引起的细胞损伤可以用自由基损伤来解释的假设是一致的，抗氧化剂通过清除自由基和抗氧化作用来保护细胞免受脂质过氧化损伤<10>。CoQ_2预处理组大鼠的存活率从0%提高到45%<10>，内毒素血症引起的细胞损伤也至少部分地由脂质过氧化引起。CoQ_2<10>和<alpha>-Toc的给药完全抑制了脂质过氧化反应，显著改善了能量代谢和内源性抗氧化剂水平，从而使存活率显著提高。少

项目成果

Sugino,K.;Dohi,K.;Yamada,K.;Kawasaki,T.: Biochim.Biophys.Acta.

Sugino，K.；Dohi，K.；Yamada，K.；川崎，T.：Biochim.Biophys.Acta。

Marubayashi, S., Dohi, K., Ochi, K., & Kawasaki, T.: "Role of free radicals in ischemic rat liver cell injury: Prevention of damage by <alpha>-tocopherol administration" Surgery. 99. 184-192 (1986)

丸林 S.、土肥 K.、大智 K.、