McCoy R N, Hill K E, Ayon M A, Stein J H, Burk R F
Department of Medicine, University of Texas Health Science Center, San Antonio 78284.
Kidney Int. 1988 Apr;33(4):812-7. doi: 10.1038/ki.1988.72.
Pretreatment of animals with certain antioxidant enzymes and substances decreases renal damage following ischemia and reperfusion. The hypothesis that reoxygenation imposes an oxidant stress has been used to explain this. The present study has directly assessed oxidant stress under these conditions by measuring the glutathione redox ratio ([GSSG/(GSH + GSSG)] x 100) in freeze-clamped kidney. The glutathione peroxidase system plays a role in removing peroxides which result from oxidant stress, generating GSSG from GSH in the process. The selenium-dependent glutathione peroxidase can metabolize H2O2 and other hydroperoxides. A non-selenium-dependent glutathione peroxidase activity is present and can metabolize organic hydroperoxides, but it cannot metabolize H2O2. Under anesthesia, the left renal artery was occluded for 40 minutes and then reflow was allowed. Kidneys were freeze clamped before reflow and after 5, 10, and 15 minutes of reflow. The contralateral kidney was freeze clamped and used as a control. The control value for the glutathione redox ratio was 1.09 +/- 0.05. This fell during ischemia to 0.67 +/- 0.22 and increased significantly to 1.66 +/- 0.29 after five minutes of reperfusion. By 15 minutes it had returned to 1.09 +/- 0.22. Treatment of rats with diquat, which causes a severe oxidant stress, raised the glutathione redox ratio from 0.88 +/- 0.12 to 1.89 +/- 0.15. Thus, reperfusion was concluded to cause a large but transient oxidant stress. Selenium-deficient rats were used to examine the nature of the oxidant stress. Activity of the selenoenzyme glutathione peroxidase was depressed to 2% of control in the kidneys of these rats.(ABSTRACT TRUNCATED AT 250 WORDS)
用某些抗氧化酶和物质对动物进行预处理可减少缺血再灌注后的肾损伤。再氧合会产生氧化应激这一假说已被用于解释此现象。本研究通过测量冷冻钳夹肾组织中的谷胱甘肽氧化还原比（[GSSG/(GSH + GSSG)]×100），直接评估了这些条件下的氧化应激。谷胱甘肽过氧化物酶系统在清除氧化应激产生的过氧化物中发挥作用，在此过程中由谷胱甘肽生成氧化型谷胱甘肽。硒依赖性谷胱甘肽过氧化物酶可代谢过氧化氢和其他氢过氧化物。存在一种非硒依赖性谷胱甘肽过氧化物酶活性，它可代谢有机氢过氧化物，但不能代谢过氧化氢。在麻醉状态下，阻断左肾动脉40分钟，然后恢复血流。在恢复血流前以及恢复血流5、10和15分钟后对肾脏进行冷冻钳夹。对侧肾脏进行冷冻钳夹并用作对照。谷胱甘肽氧化还原比的对照值为1.09±0.05。在缺血期间降至0.67±0.22，再灌注5分钟后显著升至1.66±0.29。到15分钟时已恢复至1.09±0.22。用百草枯处理大鼠，其会引起严重氧化应激，使谷胱甘肽氧化还原比从0.88±0.12升至1.89±0.15。因此，得出结论：再灌注会导致巨大但短暂的氧化应激。使用缺硒大鼠来研究氧化应激的性质。这些大鼠肾脏中硒酶谷胱甘肽过氧化物酶的活性降至对照的2%。（摘要截短于250词）
