The role of oxygen free radicals in mediating the reperfusion injury of cold-preserved ischemic kidneys.
The role of oxygen free radicals in mediating the reperfusion injury of cold-preserved ischemic kidneys.
复制标题
氧自由基在介导冷保存缺血肾脏再灌注损伤中的作用。
DOI：
10.1097/00007890-198512000-00003
复制
发表时间：
1985
期刊：
影响因子：
6.2
通讯作者：
Im,MJ
中科院分区：
文献类型：
--
作者：
Koyama,I;Bulkley,GB;Williams,GM;Im,MJ
我们在模拟人尸体肾移植的猪模型中评估了缺血后肾功能衰竭主要是由氧源性自由基再灌注引起的假设。取下两个肾脏，用Euro-Collins溶液冲洗，在4℃下保存24小时，然后移植到另一只猪身上。试验采用配对方式，每头猪接受1个治疗肾和1个对照肾。所有猪均接受水合、苯氧苄胺、呋塞米和甘露醇的最佳常规方案，以便在此基础上评估自由基治疗。两天后，通过单独的输尿管造口测量每个肾脏的肌酐清除率（CCr）。未经治疗的肾脏出现严重的功能损害，ccr从正常水平25.5\ pm6.3 ml/min （n= 8）降至7.7\pm0。9 ml/min (n= 14， P<。05 vs.对照组)。再灌注时向肾动脉输注20 mg自由基清除剂超氧化物歧化酶（SOD）可显著改善这种损伤（CCR= 15.9\pm1）。7 ml/min, n= 18，与对照组比较P< 0.05)。对SOD的剂量-反应曲线显示，0.2 mg （ccr = 8.0\pm1）剂量对SOD无影响。1 ml/min, n= 4)或2 mg (ccr = 7.7\pm 0.9, n= 5)，并且100 mg （ccr = 16.1\pm2）没有更大的益处。1 ml/min, n= 3，与对照组相比P< 0.05)。别嘌呤醇（50 mg/kg）阻断黄嘌呤氧化酶超氧自由基的产生，具有类似的保护作用（ccr = 18.2\pm1）。8;n= 11，与对照组相比P< 0.01)。另一方面，经过18小时的冷缺血后，未处理的（对照）肾脏（ccr = 22.1\pm0）受到的损伤很小。6毫升/分钟)。因此，在这些条件下，别嘌呤醇对自由基生成的消蚀没有显著的益处。这些发现表明，在冷缺血保存的关键时期后，肾脏内发生代谢变化，导致自由基的产生和随后的再灌注组织损伤，尽管传统的保存方法是最佳的。这种损害可以通过简单的无毒措施来预防，因此，这在预防尸体肾移植后的早期肾功能衰竭方面显示出很大的希望。
We evaluated the hypothesis that postischemic renal failure is caused primarily at reperfusion by oxygen-derived free radicals in a swine model designed to realistically mimick human cadaveric renal transplantation. Both kidneys were removed, flushed with Euro-Collins solution, stored 24 hr at 4† C, and then transplanted to a second pig. Experiments were paired, each pig receiving one treated and one control kidney. All pigs received the optimal conventional regimen of hydration, phenoxybenzamine, furosemide, and mannitol to allow assessment of free radical treatment superimposed thereupon. Two days later creatinine clearance (CCr) was measured from each kidney via separate ureterostomies. Untreated kidneys developed severe functional impairment, C CR falling from a normal level of 25.5\pm 6.3 ml/min (n= 8) to 7.7\pm0. 9 ml/min (n= 14, P<. 05 vs. control). The infusion of 20 mg of the free radical scavenger superoxide dismutase (SOD) into the renal artery at reperfusion substantially ameliorated this injury (CCR= 15.9\pm1. 7 ml/min, n= 18, P< 0.05 vs. control). A dose-response curve to SOD showed no effect of doses of 0.2 mg (C CR= 8.0\pm1. 1 ml/min, n= 4) or 2 mg (C CR= 7.7\pm 0.9, n= 5), and no greater benefit from 100 mg (C CR= 16.1\pm2. 1 ml/min, n= 3, P< 0.05 vs. control). Blocking the generation of superoxide radicals from xanthine oxidase with allopurinol (50 mg/kg) afforded similar protection (C CR= 18.2\pm1. 8; n= 11, P< 0.01 vs. control). On the other hand, following an 18-hr period of cold ischemia, little damage was sustained by the untreated (control) kidneys (C CR= 22.1\pm0. 6 ml/min). Consequently, under these conditions the ablation of free radical generation with allopurinol provided no significant benefit. These findings suggest that after a critical period of cold ischemic preservation, metabolic changes take place within the kidney that lead to free radical generation and consequent tissue injury upon reperfusion, despite optimal preservation by conventional methods. This damage can be prevented by simple nontoxic measures—which, therefore, show great promise for use in the prevention of early renal failure following cadaveric renal transplantation.