XANTHINE OXIDASE-MEDIATED INJURY IN ISCHEMIC LIVER

黄嘌呤氧化酶介导的缺血性肝损伤

• 批准号: 3240568
• 负责人: JULIO F TURRENS
• 金额: $ 7.98万
• 依托单位: UNIVERSITY OF SOUTH ALABAMA
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-09-30 至 1991-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3240568
• 关键词: antioxidants; enzyme mechanism; glutathione peroxidase; laboratory rat; liver circulation; liver function; liver ischemia /hypoxia; liver pharmacology; liver transplantation; reperfusion; sulfite reductase; superoxide dismutase; superoxides; tissue /cell preparation; toxin metabolism; xanthine oxidase

An important factor in preventing necrosis of transplanted liver is the ability to limit ischemia/reperfusion injury in the transplanted organ. Recent studies have established that the generation of superoxide is a critical component of ischemia/reperfusion injury in the liver. The primary source of superoxide (during reperfusion) in this tissue appears to be the enzyme xanthine oxidase. It has been proposed that xanthine oxidase is generated in ischemic tissues by conversion of native xanthine dehydrogenase, which produces is critical to the damage process. The aims of this proposal are: 1) to examine the importance of the conversion process in xanthine oxidase-mediated tissue injury in the ischemic/reperfused liver determining both the contribution of xanthine oxidase to total injury and the role of conversion in that damage, 2) to determine the mechanism of dehydrogenase to oxidase conversion in ischemic tissues examining both the processes of DTT-reversible conversion mediated by sulphydryl modification (possibly GSSG-mediated) and irreversible conversion-mediated by intracellular proteases, and 3) to examine variations in cellular antioxidant systems during ischemia that might influence tissue injury. It is hoped that these studies will provide a basis for further development of rationale pharmacological approaches to tissue preservation.

防止移植肝坏死的重要因素 是限制缺血/再灌注损伤的能力， 移植器官 最近的研究表明， 超氧化物的产生是 肝脏缺血/再灌注损伤。 的主要来源 超氧化物（再灌注期间）在这个组织似乎是 黄嘌呤氧化酶 有人提出黄嘌呤 氧化酶在缺血组织中通过转化天然的 黄嘌呤脱氢酶，它产生的是至关重要的损害 过程 这项建议的目的是：1）审查 黄嘌呤氧化酶介导的转化过程的重要性 缺血/再灌注肝脏中的组织损伤决定了 黄嘌呤氧化酶在总损伤中的作用以及 2）确定损伤的机制， 缺血组织中脱氢酶转化为氧化酶的检测 通过介导的DTT可逆转化过程 巯基修饰（可能是GSSG介导的）和不可逆的 由细胞内蛋白酶介导的转化，以及3）检查 缺血期间细胞抗氧化系统的变化， 可能会影响组织损伤。 希望这些研究将 为进一步制定理论依据提供基础 组织保存的药理学方法。