XANTHINE OXIDASE-MEDIATED INJURY IN ISCHEMIC LIVER

预防移植肝坏死的重要因素 是限制脑缺血/再灌注损伤的能力 移植的器官。最近的研究证实， 超氧化物的产生是 肝脏缺血/再灌注损伤。的主要来源 这个组织中的超氧化物(在再灌流期间)似乎是 黄嘌呤氧化酶。有人提出，黄嘌呤 在缺血组织中通过转化天然的 产生黄嘌呤脱氢酶的黄嘌呤脱氢酶对损伤至关重要 进程。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/再灌注肝脏的组织损伤决定了 黄嘌呤氧化酶在总损伤中的贡献及其作用 2)确定损伤的发生机制 缺血区组织脱氢酶向氧化物酶转化的检测 这两种DTT可逆转化过程都是由 巯基修饰(可能由GSSG介导)和不可逆性 转化--由细胞内的蛋白酶介导，以及3)检测 缺血时细胞抗氧化系统的变化 可能会影响组织损伤。希望这些研究能够 为进一步发展理论基础提供基础 组织保存的药理学方法。

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.