Lee V G, Johnson M L, Baust J, Laubach V E, Watkins S C, Billiar T R
Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
Shock. 2001 Nov;16(5):355-60. doi: 10.1097/00024382-200116050-00006.
To determine the contribution of the inducible nitric oxide synthase (iNOS) to hepatic injury following warm ischemia-reperfusion, we developed a model of partial hepatic ischemia-reperfusion in mice and studied the injury response in iNOS knockout (KO) mice. Compared with wild types, iNOS KO animals exhibited lower plasma transaminase levels after 1 and 6 h of reperfusion following 1 h of ischemia. At the 3-h time point, enzyme levels were not different between the two groups. iNOS mRNA was not detectable in the ischemic hepatic lobes of wild-type mice until 3 h of reperfusion; however, perfusion studies identified a significant delay in reperfusion of the ischemic lobe in the iNOS KO mice at the 1-h time point with similar perfusion rates at 3 and 6 h compared with wild type. By way of comparison, mice deficient in the endothelial NOS (eNOS) were also assessed for the degree of hepatic damage 3 h post-reperfusion. Plasma transaminase levels were significantly increased in eNOS KO animals compared with wild-type controls. These data suggest that systemic as well as local sources of iNOS regulate reperfusion, and local iNOS contributes to hepatic injury, while eNOS is protective in warm hepatic ischemia-reperfusion.
为了确定诱导型一氧化氮合酶（iNOS）在肝脏热缺血再灌注损伤中的作用，我们建立了小鼠部分肝脏缺血再灌注模型，并研究了iNOS基因敲除（KO）小鼠的损伤反应。与野生型相比，在缺血1小时后再灌注1小时和6小时时，iNOS基因敲除动物的血浆转氨酶水平较低。在3小时时间点，两组的酶水平没有差异。在野生型小鼠缺血肝叶中，直到再灌注3小时才检测到iNOS mRNA；然而，灌注研究发现，在1小时时间点，iNOS基因敲除小鼠缺血肝叶的再灌注明显延迟，与野生型相比，3小时和6小时时的灌注率相似。作为比较，还评估了内皮型一氧化氮合酶（eNOS）缺陷小鼠再灌注3小时后的肝损伤程度。与野生型对照相比，eNOS基因敲除动物的血浆转氨酶水平显著升高。这些数据表明，iNOS的全身和局部来源均调节再灌注，局部iNOS导致肝损伤，而eNOS在肝脏热缺血再灌注中具有保护作用。
