Regulation of postischemic liver injury following different durations of ischemia
Regulation of postischemic liver injury following different durations of ischemia
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DOI：
10.1152/ajpgi.00400.2002
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发表时间：
2003-03-01
影响因子：
4.5
通讯作者：
Grisham, MB
中科院分区：
文献类型：
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作者：
Hines, IN;Hoffman, JM;Grisham, MB
本研究的目的是确定库普弗细胞，O-2（-）的生产，和TNF-α的表达在缺血后肝损伤的病理生理学短期和长期缺血之间的关系。使用具有不同循环半衰期的不同形式的超氧化物歧化酶、针对小鼠TNF-α的单克隆抗体和NADPH氧化酶缺陷小鼠，我们发现45或90分钟的部分（70%）肝缺血和6小时的再灌注（I/R）在没有中性粒细胞浸润的情况下产生肝损伤和TNF-α表达的时间依赖性增加。此外，我们观察到，短期缺血诱导的肝细胞损伤不依赖于TNF-α的形成，而是依赖于枯否细胞和NADPH氧化酶非依赖性O-2（-）的产生。然而，长时间缺血诱导的肝损伤似乎需要枯否细胞、NADPH氧化酶衍生的O-2（-）和TNF-α表达的存在。我们的结论是O-2（-）形成的来源和TNF-α在I/R诱导的肝细胞损伤的病理生理学中的相对重要性取决于缺血的持续时间。
The objective of this study was to define the relationship among Kupffer cells, O-2(-) production, and TNF-alpha expression in the pathophysiology of postischemic liver injury following short and long periods of ischemia. Using different forms of superoxide dismutase with varying circulating half-lives, a monoclonal antibody directed against mouse TNF-alpha, and NADPH oxidase-deficient mice, we found that 45 or 90 min of partial (70%) liver ischemia and 6 h of reperfusion (I/R) produced time-dependent increases in liver injury and TNF-alpha expression in the absence of neutrophil infiltration. Furthermore, we observed that hepatocellular injury induced by short periods of ischemia were not dependent on formation of TNF-alpha but were dependent on Kupffer cells and NADPH oxidase-independent production of O-2(-). However, liver injury induced by extended periods of ischemia appeared to require the presence of Kupffer cells, NADPH oxidase-derived O-2(-), and TNF-alpha expression. We conclude that the sources for O-2(-) formation and the relative importance of TNF-alpha in the pathophysiology of I/R-induced hepatocellular injury differ depending on the duration of ischemia.