Circulating xanthine oxidase: potential mediator of ischemic injury.
Circulating xanthine oxidase: potential mediator of ischemic injury.
复制标题
循环黄嘌呤氧化酶：缺血性损伤的潜在介质。
DOI：
10.1152/ajpgi.1990.258.4.g564
复制
发表时间：
1990
期刊：
影响因子：
--
通讯作者：
Parks,DA
中科院分区：
文献类型：
--
作者：
Yokoyama,Y;Beckman,JS;Beckman,TK;Wheat,JK;Cash,TG;Freeman,BA;Parks,DA
黄嘌呤氧化酶（XO）产生的活性氧代谢物在缺血引起的组织损伤的发病机制中发挥重要作用。再灌注过程中，缺血性肝脏会释放天冬氨酸转氨酶 (AST) 和乙醇脱氢酶 (ADH) 等细胞内蛋白质，这一观察结果使我们推测 XO 可能会释放到体循环中。摘除禁食大鼠的肝脏，用含氧的 Krebs-Henseleit 缓冲液灌注，并进行 2 小时缺血，然后再灌注 2 小时。再灌注使灌注液中的 AST 从 1 +/- 1 增加到 830 +/- 280 U/l，而 ADH 从 0.3 +/- 0.1 增加到 95 +/- 26 U/l。与此同时，灌注液中的黄嘌呤脱氢酶 (XDH) + XO 活性从 0 增加至 4.1 +/- 1.0 mU/ml。内源组织 XDH + XO 活性降低 64%，与 XDH + XO 的释放平行。预计肝缺血后循环中出现的 XDH + XO 活性在提供底物时足以在体外产生严重的血管内皮损伤，即使在血清或全血存在的情况下也是如此。这些结果表明，肝缺血后大量 XDH 和 XO 释放到循环中，由此产生的活性氧代谢物可能会造成广泛的组织损伤。
Reactive oxygen metabolites generated from the enzyme xanthine oxidase (XO) play an important role in the pathogenesis of ischemia-induced tissue injury. The observation that intracellular proteins such as aspartate transaminase (AST) and alcohol dehydrogenase (ADH) are released from the ischemic liver during reperfusion led us to postulate that XO could be released into the systemic circulation. Livers from fasted rats were extirpated, perfused with oxygenated Krebs-Henseleit buffer, and subjected to 2 h ischemia followed by 2 h reperfusion. Reperfusion increased AST in the perfusate from 1 +/- 1 to 830 +/- 280 U/l, whereas ADH increased from 0.3 +/- 0.1 to 95 +/- 26 U/l. Concomitantly, xanthine dehydrogenase (XDH) + XO activity in the perfusate increased from 0 to 4.1 +/- 1.0 mU/ml. A 64% decrease in endogenous tissue XDH + XO activity paralleled release of XDH + XO. The XDH + XO activity predicted to appear in the circulation after hepatic ischemia was sufficient, when supplied with substrate, to produce severe vascular endothelial injury in vitro, even in the presence of serum or whole blood. These results suggest that massive quantities of XDH and XO are released into the circulation after hepatic ischemia and that the resulting reactive oxygen metabolites could produce widespread tissue injury.