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 强化饮食使肺 XD 和 XO 消耗了 80%。使用这些大鼠的离体灌注肺，进行90分钟的缺血和再灌注。与正常大鼠的肺相比，XO 缺陷大鼠的肺免受缺血再灌注损伤。 XO 抑制剂别嘌呤醇也能有效保护肺部免受缺血再灌注。因此很明显XO介导肺缺血再灌注损伤。另一项实验中，SOD和氧自由基清除剂过氧化氢酶也能保护肺免受60分钟缺血再灌注损伤，这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 分钟时没有发生 XD 到 XO 的转化。此外，缺血期间持续通气 100 N2 可减少缺血再灌注肺损伤。这些结果表明，XO不太可能是再灌注后氧自由基的主要来源。最近的报道表明，缺血再灌注后氧自由基的主要来源是多形核白细胞（PMN）和组织固定巨噬细胞。此外，Terada 报道称，钨酸盐饮食可以防止肠道缺血后白细胞在肺部积聚。因此，XD 和 XO 可能有助于缺血再灌注期间 PMN 的激活。