Reperfusion injury pathophysiology in sickle transgenic mice

作     者：Osarogiagbon, UR Choong, S Belcher, JD Vercellotti, GM Paller, MS Hebbel, RP 

作者机构：Univ Minnesota Sch Med Dept Med Minneapolis MN 55455 USA 

出 版 物：《BLOOD》 (血液)

年 卷 期：2000年第96卷第1期

页      面：314-320页

核心收录：

学科分类：1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 10[医学] 

基　　金：NHLBI NIH HHS [P01 HL055552  P01-HL55552] Funding Source: Medline 

主　　题：别嘌呤醇/治疗应用 贫血 镰状细胞性/药物疗法 贫血 镰状细胞性/遗传学 贫血 镰状细胞性/病理生理学 酶抑制剂/治疗应用 乙烷/分析 血红蛋白 镰状/遗传学 羟自由基/代谢 肾/代谢 脂质过氧化作用 肝/代谢 小鼠 近交C57BL 小鼠 转基因 NF-κB/代谢 参考值 再灌注损伤/病理生理学 水杨酸/药代动力学 黄嘌呤脱氢酶/代谢 黄嘌呤氧化酶/代谢 动物 人类 小鼠 

摘      要：Reperfusion of tissues after interruption of their vascular supply causes free-radical generation that leads to tissue damage, a scenario referred to as reperfusion Injury. Because sickle disease involves repeated transient ischemic episodes, we sought evidence for excessive free-radical generation in sickle transgenic mice. Compared with normal mice, sickle mice at ambient air had a higher ethane excretion (marker of lipid peroxidation) and greater conversion of salicylic acid to 2,3-dihydroxybenzoic acid (marker of hydroxyl radical generation). During hypoxia (11% O-2), only sickle mice converted tissue xanthine dehydrogenase to oxidase. Only the sickle mice exhibited a further increase in ethane excretion during restitution of normal oxygen tension after 2 hours of hypoxia. Only the sickle mice showed abnormal activation of nuclear factor-kappa B after exposure to hypoxia-reoxygenation. Allopurinol, a potential therapeutic agent, decreased ethane excretion in the sickle mice. Thus, sickle transgenic mice exhibit biochemical foot-prints consistent with excessive free-radical generation even at ambient air and following a transient induction of enhanced sickling. We suggest that reperfusion injury physiology may contribute to the evolution of the chronic organ damage characteristic of sickle cell disease. If so, novel therapeutic approaches might be of value. (Blood. 2000;96:314-320) (C) 2000 by The American Society of Hematology.