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Cell protection of allopurinol during ischemia-reperfusion in the lung.

别嘌呤醇在肺缺血再灌注过程中的细胞保护作用。

基本信息

批准号：
05671258
负责人：
OKUDA Masahiro
金额：
$ 1.28万
依托单位：
MIE UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05671258/
关键词：
Lung Ischemia-Reperfusion Injury Free Rdical Xanthine Oxidase 虚血再灌流障害虚血再潅流

项目摘要

Tangstate enriched diet for 3-4 weeks depleted the lung XD and XO by 80%. Using isolated perfused lungs of these rats, 90 minutes ischemia and reperfusion were performed. The lungs of XO deficient rats were protected from ischemia reperfusion injury as compared with the lungs of normal rats. Allopurinol, XO inhibitor was also effective to protect the lungs from ischemia-reperfusion. Therefore it is clear that XO mediates ischemia-reperfusion injury in the lung. In another experiment, SOD and catalase, oxygen radical scavenger, also protected the lungs from 60 minutes ischemia and reperfusion, which indicates that oxygen radicals involves in lung ischemia-reperfusion injury. On the other hand, we found that XD to XO conversion was not occurred by 90 minutes ischemia. Moreover, continuous ventilation during ischemia with 100 N2 decreased ischemia-reperfusion lung injury. These results suggest that XO is unlikely to be a main source of oxygen radical after reperfusion.Recent reports demonstrated that the main source of oxygen radicals after ischemia-reperfusion was polymorphonuclear leukocyte (PMN) and tissue fixed macrophage. In addition, Terada reported that tungstate diet prevent leukocyte accumulation in the lung after intestinal ischemia. Therefore, XD and XO may contribute to PMN activation during ischemia-reperfusion.

3-4周的Tangstate强化饮食消耗了80%的肺XD和XO。采用离体肺灌流，进行90分钟缺血再灌注。与正常大鼠相比，XO缺陷大鼠肺对缺血再灌注损伤具有保护作用。XO抑制剂别嘌呤醇对肺缺血再灌注损伤也有保护作用。因此，很明显，XO介导肺缺血-再灌注损伤。在另一实验中，SOD和过氧化氢酶（氧自由基清除剂）也对肺缺血再灌注60分钟有保护作用，表明氧自由基参与了肺缺血再灌注损伤。另一方面，我们发现缺血90分钟后，XD尚未发生向XO的转化。此外，在缺血期间用100 N2持续通气减少缺血再灌注肺损伤。这些结果表明XO不是再灌注后氧自由基的主要来源，最近的研究表明，缺血再灌注后氧自由基的主要来源是多形核白细胞（PMN）和组织固定的巨噬细胞。此外，Terada报道，钨酸盐饮食可防止肠缺血后肺中白细胞积聚。因此，XD和XO可能有助于在缺血再灌注期间激活PMN。