Rymsa B, Wang J F, de Groot H
Klinische Forschergruppe Leberschädigung, Institut für Physiologische Chemie I, Heinrich-Heine-Universität, Düsseldorf, Federal Republic of Germany.
Am J Physiol. 1991 Oct;261(4 Pt 1):G602-7. doi: 10.1152/ajpgi.1991.261.4.G602.
Primary cultures of rat liver Kupffer cells generated large amounts of superoxide anion radical (O2-.) when subjected to reoxygenation after a hypoxic period of at least 2 h. O2-. formation reached its maximum rate of approximately 25 nmol/10(6) cells within 1 h after reoxygenation. Two to four hours after reoxygenation, the number of injured cells began to increase and after 10 h approximately 60% of the cells were dead. During the period of O2-. release no significant difference in cell viability was observed between reoxygenated and hypoxically incubated cells, indicating a distinct time lag between O2-. release and onset of cell damage. Addition of diphenyliodonium, a specific inhibitor of the neutrophilic NADPH oxidase, to the Kupffer cells just before reoxygenation diminished both O2-. formation and cell injury up to 70%. Reoxygenation injury was completely prevented when superoxide dismutase and catalase were added immediately before reoxygenation. The results indicate that Kupffer cells subjected to hypoxia-reoxygenation generate a burst of reactive oxygen species and that this kind of "activation," probably by activating the NADPH oxidase, contributes to the self-destruction of the cells.
大鼠肝脏库普弗细胞的原代培养物在经历至少2小时的缺氧期后再进行复氧时，会产生大量超氧阴离子自由基（O2-.）。复氧后1小时内，O2-.的生成达到其最大速率，约为25 nmol/10(6)个细胞。复氧后2至4小时，受损细胞数量开始增加，10小时后约60%的细胞死亡。在O2-.释放期间，复氧细胞和缺氧孵育细胞之间未观察到细胞活力的显著差异，这表明O2-.释放与细胞损伤开始之间存在明显的时间滞后。在复氧前向库普弗细胞中加入中性粒细胞NADPH氧化酶的特异性抑制剂二苯基碘鎓，可使O2-.生成和细胞损伤减少高达70%。当在复氧前立即加入超氧化物歧化酶和过氧化氢酶时，复氧损伤可完全预防。结果表明，经历缺氧-复氧的库普弗细胞会产生一阵活性氧，这种“激活”可能是通过激活NADPH氧化酶，导致细胞自我破坏。
