Favorable balance of anti-oxidant/pro-oxidant systems and ablated oxidative stress in Brown Norway rats in renal ischemia-reperfusion injury
Favorable balance of anti-oxidant/pro-oxidant systems and ablated oxidative stress in Brown Norway rats in renal ischemia-reperfusion injury
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DOI：
10.1007/s11010-007-9480-z
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发表时间：
2007-10-01
影响因子：
4.3
通讯作者：
Shames, Brian D.
中科院分区：
文献类型：
--
作者：
Nilakantan, Vani;Hilton, Gail;Shames, Brian D.
氧化应激在肾缺血-再灌注损伤的发病机制中起重要作用，然而活性氧产生和处理的不平衡是否导致了损伤的易感性尚不清楚。本研究的目的是在肾IR损伤的体内模型中比较IR抵抗的Brown Norway大鼠与IR敏感的Sprague-道利（SD）大鼠的坏死、凋亡和氧化应激。由于超氧阴离子（O-2（-））与一氧化氮（NO）相互作用形成过氧亚硝基阴离子，还检测了诱导型NO合酶（iNOS）和硝基酪氨酸。SD和BN大鼠通过双侧肾动脉夹闭45 min，然后再灌注24 h（分别为SD 24和BN 24）来诱导肾IR。BN大鼠对肾IR损伤具有抵抗力，这通过较低的血浆肌酐和减少的急性肾小管坏死来证明。IR后BN大鼠肾组织中O-2（-）水平显著低于SD大鼠（P < 0.05），O-2（-）歧化蛋白CuZn SOD（P < 0.05）也显著低于SD大鼠（P < 0.05）。这伴随着BN中4-羟基壬烯醛加合物的总体减少，但在IR后的SD大鼠中没有。BN大鼠也显示出较低的iNOS表达（P < 0.05）导致组织NO水平降低和硝基酪氨酸形成减少（P < 0.01）。总的来说，这些结果表明BN大鼠对肾IR损伤的抵抗力与氧化剂的有利平衡有关。生产与氧化剂去除。
Oxidative stress is important in the pathogenesis of renal ischemia- reperfusion ( IR) injury; however whether imbalances in reactive oxygen production and disposal account for susceptibility to injury is unclear. The purpose of this study was to compare necrosis, apoptosis, and oxidative stress in IR- resistant Brown Norway rats vs. IR- susceptible Sprague- Dawley ( SD) rats in an in vivo model of renal IR injury. As superoxide ( O-2(-)) interacts with nitric oxide ( NO) to form peroxynitrite, inducible NO synthase ( iNOS) and nitrotyrosine were also examined. Renal IR was induced in SD and BN rats by bilateral clamping of renal arteries for 45 min followed by reperfusion for 24 h ( SD 24 and BN 24, respectively). BN rats were resistant to renal IR injury as evidenced by lower plasma creatinine and decreased acute tubular necrosis. TUNEL staining analysis demonstrated significantly decreased apoptosis in the BN rats vs. SD rats after IR. Following IR, O-2(-) levels were also significantly lower in renal tissue of BN rats vs. SD rats ( P < 0.05) in conjunction with a preservation of the O-2(-) dismutating protein, CuZn superoxide dismutase ( CuZn SOD) ( P < 0.05). This was accompanied by an overall decrease in 4- hydroxynonenal adducts in the BN but not SD rats after IR. BN rats also displayed lower iNOS expression ( P < 0.05) resulting in lower tissue NO levels and decreased nitrotyrosine formation ( P < 0.01) following IR. Collectively these results show that the resistance of the BN rat to renal IR injury is associated with a favorable balance of oxidant production vs. oxidant removal.