Oxidant stress following renal ischemia: changes in the glutathione redox ratio.
Oxidant stress following renal ischemia: changes in the glutathione redox ratio.
复制标题
肾缺血后的氧化应激：谷胱甘肽氧化还原比的变化。
DOI：
10.1038/ki.1988.72
复制
发表时间：
1988
影响因子：
19.6
通讯作者：
Burk,RF
中科院分区：
文献类型：
--
作者：
McCoy,RN;Hill,KE;Ayon,MA;Stein,JH;Burk,RF
肾缺血后的氧化应激：谷胱甘肽氧化还原比的变化。用某些抗氧化酶和物质预处理动物可减少缺血和再灌注后的肾损伤。再氧合施加氧化应激的假说已被用来解释这一点。本研究通过测定冷冻夹闭肾脏中谷胱甘肽氧化还原比（[GSSG/（GSH + GSSG）] × 100）来直接评估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起作用，在此过程中从GSH产生GSSG。硒依赖的谷胱甘肽过氧化物酶能代谢H2 O2和其它氢过氧化物。存在非硒依赖性谷胱甘肽过氧化物酶活性，可代谢有机氢过氧化物，但不能代谢H2 O2。在麻醉下，将左肾动脉闭塞40分钟，然后允许复流。在再流前和再流5、10和15分钟后冷冻夹闭肾脏。对侧肾脏被冷冻夹闭并用作对照。谷胱甘肽氧化还原比的对照值为1.09 ± 0.05。在缺血期间下降到0.67 ± 0.22，再灌注5分钟后显著增加到1.66 ± 0.29。到15分钟时，它已恢复到1.09 ± 0.22。用敌草快（引起严重的氧化应激）治疗大鼠，使谷胱甘肽氧化还原比从0.88 ± 0.12提高到1.89 ± 0.15。因此，再灌注的结论是造成一个大的，但短暂的氧化应激。硒缺乏大鼠被用来检查氧化应激的性质。硒酶谷胱甘肽过氧化物酶的活性被抑制到2%的控制在这些大鼠的肾脏。再灌注使谷胱甘肽氧化还原比从0.79 ± 0.09升高至1.17 ± 0.30。这是一个较小的增加比发生在富硒肾脏。这些结果表明，H_2O_2在富硒肾GSSG形成中起主要作用。丙二醛进行了测量，并没有增加检测到在富硒肾脏，这表明很少发生脂质过氧化反应的氧化应激的结果。本研究的结果提供了直接的证据，氧化应激过程中的肾脏缺血后再灌注，并表明H2 O2的产生。
Oxidant stress following renal ischemia: Changes in the glutathione redox ratio. 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)] × 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 H2O2and 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. Reperfusion raised the glutathione redox ratio from 0.79 ± 0.09 to 1.17 ± 0.30. This was a smaller increase than occurred in the selenium-replete kidneys. These results suggest that H2O2was largely responsible for GSSG formation in selenium-replete kidneys. Malondialdehyde was measured, and no increase was detected in selenium-replete kidneys, suggesting that little lipid peroxidation occurred as a result of the oxidant stress. The results of this study provide direct evidence for an oxidant stress during reperfusion of the kidney after ischemia and indicate that H2O2was produced.