NEUTROPHIL AND KUPFFER CELL-INDUCED OXIDANT STRESS AND ISCHEMIA-REPERFUSION INJURY IN RAT-LIVER
NEUTROPHIL AND KUPFFER CELL-INDUCED OXIDANT STRESS AND ISCHEMIA-REPERFUSION INJURY IN RAT-LIVER
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DOI：
10.1152/ajpgi.1991.260.3.g355
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发表时间：
1991-03-01
影响因子：
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通讯作者：
FARHOOD, A
中科院分区：
文献类型：
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作者：
JAESCHKE, H;FARHOOD, A
在雄性Fischer大鼠体内部分无血流缺血和再灌注模型中，研究了枯否细胞和浸润中性粒细胞在肝窦中产生活性氧并可能导致肝脏缺血-再灌注损伤的假设。在60分钟的再灌注期间，血浆谷胱甘肽二硫化物浓度（GSSG;氧化应激指数）从1.62 +/- 0.20 μ M谷胱甘肽（GSH）当量增加到最大值11.82 +/- 1.45（45分钟缺血）、24.19 +/-2.35（60分钟缺血）和70.20 +/-7.8（120分钟缺血）。缺血后叶中的基底组织GSSG含量（0.19 +/- 0.02 nmol GSH eq/mg蛋白）增加了50- 100%。虽然在肝脏和肺中的中性粒细胞的数量增加了3至10倍，在再灌注期间，有中性粒细胞的数量和血浆或组织中测得的GSSG浓度之间没有正相关性。然而，激活枯否细胞与高剂量的视黄醇或痤疮丙酸杆菌显着增强血浆GSSG水平，而灭活枯否细胞与棕榈酸甲酯或氯化钆显着衰减血浆GSSG的增加。枯否细胞的失活对肝脏缺血再灌注损伤有明显的保护作用。可以得出结论，枯否细胞是在初始再灌注期间形成的活性氧的主要来源，枯否细胞活性（包括活性氧形成）有助于在体内肝脏再灌注损伤。
The hypothesis that Kupffer cells and infiltrating neutrophils generate reactive oxygen in the hepatic sinusoids and may contribute to ischemia-reperfusion injury in the liver was investigated in a model of partial no-flow ischemia and reperfusion in male Fischer rats in vivo. During the reperfusion period of 60 min, plasma concentrations of glutathione disulfide (GSSG; index of oxidant stress) increased from 1.62 +/- 0.20-mu-M glutathione (GSH) equivalents to maximal values of 11.82 +/- 1.45 (45 min ischemia), 24.19 +/- 2.35 (60 min ischemia), and 70.20 +/- 7.8 (120 min ischemia). The basal tissue GSSG content in the postischemic lobes (0.19 +/- 0.02 nmol GSH eq/mg protein) increased by 50-100%. Although the number of neutrophils in liver and lung increased by 3- to 10-fold during reperfusion, there was no positive correlation between the number of neutrophils and the GSSG concentrations measured in plasma or tissue. However, activation of Kupffer cells with high doses of retinol or with Propionibacterium acnes significantly enhanced plasma GSSG levels, while inactivation of Kupffer cells with methyl palmitate or gadolinium chloride significantly attenuated the increase of plasma GSSG. Inactivation of Kupffer cells protected the liver significantly against ischemia-reperfusion injury. It is concluded that Kupffer cells are the predominant source of reactive oxygen formed during the initial reperfusion period and that Kupffer cell activity (including reactive oxygen formation) contributes to reperfusion injury in the liver in vivo.