Acute alcohol produces hypoxia directly in rat liver tissue in vivo: Role of Kupffer cells
Acute alcohol produces hypoxia directly in rat liver tissue in vivo: Role of Kupffer cells
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DOI：
10.1152/ajpgi.1996.271.3.g494
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发表时间：
1996-09-01
影响因子：
4.5
通讯作者：
Thurman, RG
中科院分区：
文献类型：
--
作者：
Arteel, GE;Raleigh, JA;Thurman, RG
先前使用肝切片和离体灌注大鼠肝脏的研究表明，乙醇通过增加耗氧量导致缺氧。然而，乙醇也会增加肝脏的血流量，这种现象可能会通过增加氧气输送来抵消代谢亢进的影响。因此乙醇是否会导致体内缺氧仍不清楚。为了阐明这一重要点，雌性 Sprague-Dawley 大鼠（100-125 g）同时接受哌莫硝唑（120 mg/kg ip）（一种 2-硝基咪唑缺氧标记物）和大剂量乙醇（5 g/kg ig），这会在 2-3 天内显着增加肝脏摄氧量并提高乙醇代谢（酒精代谢迅速增加）。 h. 2小时后，乙醇显着增加了肝小叶中央区域结合哌莫硝唑的积累。用库普弗细胞特异性毒剂 GdCl3（10 mg/kg 静脉注射，实验前 24 小时）处理动物，可阻止乙醇诱导的哌莫硝唑结合增加。结论是大剂量乙醇引起体内大鼠肝组织中枢周围缺氧，库普弗细胞参与其中。
Previous studies using liver slices and isolated perfused rat liver have suggested that ethanol causes hypoxia by increasing oxygen consumption. However, ethanol also increases blood flow to the liver, a phenomenon that may counteract the effects of hypermetabolism by increasing oxygen delivery. Thus whether ethanol causes hypoxia in vivo remains unclear. To clarify this important point, female Sprague-Dawley rats (100-125 g) simultaneously received pimonidazole (120 mg/kg ip), a 2-nitroimidazole hypoxia marker, and one large dose of ethanol (5 g/kg ig), which increase hepatic oxygen uptake dramatically and elevate ethanol metabolism (swift increase in alcohol metabolism) in 2-3 h. After 2 h, ethanol significantly increased the accumulation of bound pimonidazole in pericentral regions of the liver lobule. Treatment of animals with the Kupffer cell-specific toxicant, GdCl3 (10 mg/kg iv, 24 h before experiment), blocked ethanol-induced increases in pimonidazole binding. It is concluded that one large dose of ethanol causes pericentral hypoxia in rat liver tissue in vivo and that Kupffer cells are involved.