Exacerbation of alcoholic liver injury by enteral endotoxin in rats
Exacerbation of alcoholic liver injury by enteral endotoxin in rats
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DOI：
10.1053/jhep.2000.19621
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发表时间：
2000-11-01
期刊：
影响因子：
13.5
通讯作者：
Tsukamoto, H
中科院分区：
文献类型：
--
作者：
Mathurin, P;Deng, QG;Tsukamoto, H
肠通透性增加（漏肠）和内毒素介导的枯否细胞活化被认为是酒精性肝损伤的机制。虽然乙醇喂养被证明是敏感的肝脏肠外脂多糖（LPS）诱导的损伤，肠内脂多糖负荷如何影响酒精性肝损伤还有待测试。本研究提供了直接的证据，增强入口门静脉循环的LPS肠内给药的乙醇灌注模型。在酒精喂养的动物中，肠内给予LPS（5 mg/kg）后2小时，门静脉和全身血液内毒素水平增加至43.0 +/- 4.1和6.2 +/- 4.3 pg/mL，而在成对喂养的对照组中未观察到此类增加。然而，在给予LPS后16小时，酒精喂养大鼠的全身血液中的内毒素水平降低至0至1.5 pg/mL。每周肠内给予LPS 9周，可加重血浆丙氨酸转氨酶（ALT）水平的升高（227 ± 75 vs. 140 ± 70; P
Increased gut permeability (leaky gut) and endotoxin-mediated Kupffer cell activation are proposed as the mechanisms of alcoholic liver injury. Although ethanol feeding is shown to sensitize the liver for injury induced by parental administration of lipopolysaccharide (LPS), how enteral LPS loading affects alcoholic liver injury is yet to be tested. The present study provides direct evidence for enhanced entrance to portal circulation of LPS enterally administered to the intragastric ethanol infusion model. Portal and systemic blood endotoxin levels increased to 43.0 +/- 4.1 and 6.2 +/- 4.3 pg/mL at 2 hours following enteral LPS administration (5 mg/kg) in alcohol-fed animals, while no such increases were observed in pair-fed controls. However, endotoxin levels in systemic blood of alcohol-fed rats were reduced to 0 to 1.5 pg/mL 16 hours after LPS administration. Weekly enteral administration of LPS to the model for 9 weeks exacerbated an increase in plasma alanine transaminase (ALT) levels (227 +/- 75 vs. 140 +/- 70; P