Grune T, Schneider W, Siems W G
Klinik für Physikalische Medizin und Rehabilitation, Humboldt Universität zu Berlin, Federal Republic of Germany.
Cell Mol Biol (Noisy-le-grand). 1993 Sep;39(6):635-50.
Isolated rat hepatocytes were used for the evaluation of nucleotide depletion and oxidative stress as two causal components of postischemic injury following oxygen deficiency. The ATP and GTP loss during anoxia was accompanied by temporary increases of nucleotide degradation products. The critical duration of anoxia for a complete ATP restoration during reoxygenation was between 30 and 60 min. The oxidative stress during reoxygenation was demonstrated by decrease of GSH concentration and increase of TBA-RS level. The tremendous GSH loss could not be balanced by the slight GSSG increase during reoxygenation. Prevention of GSH decrease and TBA-RS increase in parallel to prevention of viability loss in presence of oxipurinol in contrast to lacking improvement of ATP and GTP restoration by this drug speak in favor for the oxidative stress as major causal component for postischemic injury of hepatocytes in comparison with depletion of energy-rich purine nucleotides. The inhibition of formation of reactive oxygen species via xanthine oxidase reactions was found to be the dominant protective effect of oxipurinol against postischemic injury of hepatocytes in comparison with lacking influence on nucleotide salvage and ATP/GTP regeneration and with radical scavenging.
分离的大鼠肝细胞用于评估核苷酸耗竭和氧化应激，这两者是缺氧后缺血性损伤的两个致病因素。缺氧期间ATP和GTP的损失伴随着核苷酸降解产物的暂时增加。复氧期间完全恢复ATP的关键缺氧持续时间在30至60分钟之间。复氧期间的氧化应激通过谷胱甘肽（GSH）浓度降低和硫代巴比妥酸反应物（TBA-RS）水平升高得以证明。复氧期间GSH的大量损失无法通过GSSG的轻微增加来平衡。与该药物未能改善ATP和GTP恢复相反，在存在奥昔嘌醇的情况下，防止GSH降低和TBA-RS增加与防止活力丧失同时发生，这表明与富含能量的嘌呤核苷酸耗竭相比，氧化应激是肝细胞缺血性损伤的主要致病因素。与对核苷酸补救和ATP/GTP再生缺乏影响以及自由基清除作用相比，发现通过黄嘌呤氧化酶反应抑制活性氧的形成是奥昔嘌醇对肝细胞缺血性损伤的主要保护作用。
