Effects of xanthine oxidase inhibition on ischemic acute renal failure in the rat.
Effects of xanthine oxidase inhibition on ischemic acute renal failure in the rat.
复制标题
黄嘌呤氧化酶抑制对大鼠缺血性急性肾衰竭的影响。
DOI：
10.1152/ajprenal.1989.257.6.f953
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发表时间：
1989
期刊：
影响因子：
--
通讯作者：
Gmur,DJ
中科院分区：
文献类型：
--
作者：
Zager,RA;Gmur,DJ
为了评估黄嘌呤氧化酶（XO）抑制对缺血性损伤的影响，大鼠预先用氧嘌呤醇（OXY，5 mg/kg），并进行30分钟的双侧肾动脉闭塞。在缺血10和30分钟以及再灌注期间（5和30分钟）测定OXY对腺嘌呤核苷酸-核苷-嘌呤碱浓度的影响。为了评估XO介导的氧化应激是否影响缺血性急性肾衰竭（IARF）的严重程度，评估了1）OXY预处理和2）次黄嘌呤输注的效果。在缺血OXY抑制XO活性（超过四倍的次黄嘌呤-黄嘌呤比率上升），并诱导ATP和总腺嘌呤核苷酸浓度（30分钟）的定量微不足道，但显着增加。增加OXY剂量（15 mg/kg）或别嘌呤醇（40 mg/kg）没有更大的影响。在5分钟的复流，氧维持XO抑制，但不影响腺嘌呤核苷酸水平。回流30分钟后，ATP-总腺嘌呤核苷酸增加17-20%。然而，氧合并没有减轻IARF的严重程度（通过24小时的氮质血症组织学评估）。次黄嘌呤输注使缺血终末次黄嘌呤浓度增加47%，但不改变肾损害的严重程度。结论包括：1）OXY-别嘌呤醇诱导肾内XO抑制; 2）XO抑制剂轻微增加晚期缺血-再灌注腺嘌呤核苷酸浓度; 3）XO抑制和肾内次黄嘌呤负荷均不改变IARF的严重程度，表明XO介导的氧化应激不是缺血性肾损伤的关键、一致的介质。
To assess the effects of xanthine oxidase (XO) inhibition on ischemic injury, rats were pretreated with oxypurinol (OXY, 5 mg/kg) and subjected to 30 min of bilateral renal artery occlusion. OXY's effect on adenine nucleotide-nucleoside-purine base concentrations was determined at 10 and 30 min of ischemia and during reperfusion (5 and 30 min). To assess whether XO-mediated oxidant stress influences the severity of ischemic acute renal failure (IARF), the effects of 1) OXY pretreatment and 2) hypoxanthine infusion were assessed. During ischemia OXY inhibited XO activity (more than fourfold rise in hypoxanthine-xanthine ratios) and induced quantitatively trivial but significant increases in ATP and total adenine nucleotide concentrations (by 30 min). Increased OXY dosage (15 mg/kg) or allopurinol (40 mg/kg) had no greater effects. At 5 min of reflow, OXY maintained XO inhibition but did not influence adenine nucleotide levels. By 30 min of reflow, 17–20% increments in ATP-total adenine nucleotides resulted. Nevertheless, OXY did not lessen the severity of IARF (assessed by azotemia-histology at 24 h). Hypoxanthine infusion increased end-ischemic hypoxanthine concentrations by 47%, but it did not change the severity of renal damage. Conclusions include 1) OXY-allopurinol induces intrarenal XO inhibition; 2) XO inhibitors slightly increase late ischemic-reperfusion adenine nucleotide concentrations; and 3) neither XO inhibition nor intrarenal hypoxanthine loading alters the severity of IARF, suggesting that XO-mediated oxidant stress is not a critical, consistent mediator of ischemic renal injury.