期刊
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
卷 292, 期 5, 页码 G1385-G1395出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpgi.00246.2006
关键词
liver blood flow; microvascular dysfunction; heme oxygenase-1; neutrophils; hypochlorous acid; steatosis
资金
- Austrian Science Fund FWF [P 17013] Funding Source: Medline
- Intramural NIH HHS Funding Source: Medline
- NIAAA NIH HHS [R01 AA012436, R01 AA012916, AA-12436, R56 AA012916, AA-12916] Funding Source: Medline
- NIDDK NIH HHS [R01 DK070195, DK-070195] Funding Source: Medline
Steatosis is a major risk factor for complications after liver surgery. Since neutrophil cytotoxicity is critical for ischemia-reperfusion injury in normal livers, the aim of the present study was to evaluate whether an exaggerated inflammatory response could cause the increased injury in steatotic livers. In C57B1/6 mice, 60 min of warm hepatic ischemia triggered a gradual increase in hepatic neutrophil accumulation during reperfusion with peak levels of 100- fold over baseline at 12 h of reperfusion. Neutrophil extravasation and a specific neutrophil-induced oxidant stress ( immunostaining for hypochlorous acid- modified epitopes) started at 6 h of reperfusion and peaked at 12 - 24 h. Ob/ob mice, which had a severe macrovesicular steatosis, suffered significantly higher injury ( alanine transaminase activity: 18,000 +/- 2,100 U/1; 65% necrosis) compared with lean littermates ( alanine transaminase activity: 4,900 +/- 720 U/1; 24% necrosis) at 6 h of reperfusion. However, 62% fewer neutrophils accumulated in steatotic livers. This correlated with an attenuated increase in mRNA levels of several proinflammatory genes in ob/ ob mice during reperfusion. In contrast, sham- operated ob/ ob mice had a 50% reduction in liver blood flow and 35% fewer functional sinusoids compared with lean littermates. These deficiencies in liver blood flow and the microcirculation were further aggravated only in ob/ ob mice during reperfusion. The attenuated inflammatory response and reduced neutrophil- induced oxidant stress observed in steatotic livers during reperfusion cannot be responsible for the dramatically increased injury in ob/ ob mice. In contrast, the aggravated injury appears to be mediated by ischemic necrosis due to massive impairment of blood and oxygen supply in the steatotic livers.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据