Oxidative stress and reactive nitrogen species generation during renal ischemia
Oxidative stress and reactive nitrogen species generation during renal ischemia
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DOI：
10.1093/toxsci/63.1.143
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发表时间：
2001-09-01
影响因子：
3.8
通讯作者：
Mayeux, PR
中科院分区：
文献类型：
--
作者：
Walker, LM;York, JL;Mayeux, PR
以往的研究表明，氧自由基和一氧化氮（NO）都是肾缺血再灌注（I-R）损伤的重要介质。然而，在早期时间点，尚未在该模型中评价活性氮物质（RNS）的产生。这些研究的目的是检查I-R损伤期间氧化应激的发展和RNS的形成。将雄性Sprague-Dawley大鼠麻醉并进行40分钟的双侧肾缺血，随后进行0、3或6小时的再灌注。对照组动物接受假手术。监测血浆尿素氮和肌酐水平作为肾损伤的标志物。谷胱甘肽（GSH）氧化和4-羟基壬烯醛（4-HNE）-蛋白加合物被用作氧化应激的标志物。3-硝基酪氨酸（3-NT）被用作RNS形成的生物标志物。血浆肌酐浓度和尿素氮水平显着增加，发现后3和6小时的再灌注。GSH氧化，4-HNE-蛋白加合物水平，3-NT水平的增加，观察缺血40分钟后，没有再灌注。由于这些结果表明在缺血40分钟期间产生RNS，因此评价了缺血0、5、10、20和40分钟后RNS产生的时间过程。早在缺血10分钟时就检测到3-NT生成的显著增加，并且在缺血40分钟时升至比对照高近10倍的值。再灌注后未观察到额外的增加。数据清楚地表明，氧化应激和RNS的产生发生在肾缺血期间。
Previous evidence suggests that both oxygen radicals and nitric oxide (NO) are important mediators of injury during renal ischemia-reperfusion (I-R) injury. However, the generation of reactive nitrogen species (RNS) has not been evaluated in this model at early time points. The purpose of these studies was to examine the development of oxidant stress and the formation of RNS during I-R injury. Male Sprague-Dawley rats were anesthetized and subjected to 40 min of bilateral renal ischemia followed by 0, 3, or 6 h of reperfusion. Control animals received a sham operation. Plasma urea nitrogen and creatinine levels were monitored as markers of renal injury. Glutathione (GSH) oxidation and 4-hydroxynonenal (4-HNE)-protein adducts were used as markers of oxidant stress. 3-Nitrotyrosine (3-NT) was used as a biomarker of RNS formation. Significant increases in plasma creatinine concentrations and urea nitrogen levels were found following both 3 and 6 h of reperfusion. Increases in GSH oxidation, 4-HNE-protein adduct levels, and 3-NT levels were observed following 40 min of ischemia with no reperfusion. Since these results suggested RNS generation during the 40 min of ischemia, a time course of RNS generation following 0, 5, 10, 20, and 40 min of ischemia was evaluated. Significant increases in 3-NT generation was detected as early as 10 min of ischemia and rose to values nearly 10-fold higher than Control at 40 min of ischemia. No additional increase was observed following reperfusion. The data clearly demonstrate that oxidative stress and RNS generation occur in the kidney during ischemia.