Bautista A P, Spitzer J J
Department of Physiology, Louisiana State University Medical Center, New Orleans 70112, USA.
Alcohol Clin Exp Res. 1996 Nov;20(8):1395-400. doi: 10.1111/j.1530-0277.1996.tb01139.x.
This study tests two hypotheses: (1) prior exposure to LPS induces cross-tolerance for the hepatic effects of subsequent short-term alcohol intoxication; and (2) short-term alcohol intoxication renders the liver resistant to the effects of acute endotoxemia, resulting in reduced production of superoxide and tumor necrosis factor. In the first group of experiments, male Sprague-Dawley rats were treated intravenously with E. coli lipopolysaccharide (LPS) (0.5 mg/kg) 48 hr before they were given an intravenous bolus of ethanol (1.75 g/kg), followed by 250-300 mg/kg/hr) for 3-5 hr. Superoxide release in the perfused liver was measured after 3-hr ethanol infusion. Pretreatment with LPS attenuated ethanol-mediated superoxide anion release by the perfused liver. The stimulatory effect of phorbol myristate acetate on hepatic release of superoxide was also decreased. In the second group of experiments, rats previously treated with ethanol for 5 hr, received an intravenous injection of LPS (1 mg/kg). At 90 min after LPS, sera were collected for tumor necrosis factor alpha assay. Hepatic release of superoxide anion was determined 3 hr after LPS. Acute ethanol intoxication for 5 hr significantly reduced LPS-induced serum tumor necrosis factor activity and free radical release by the perfused liver. LPS-induced mortality was also decreased. In both groups of experiments serum corticosteroid levels were reduced during cross-tolerance. These results demonstrate that cross-tolerance develops between acute alcohol intoxication and endotoxemia manifesting in reduced hepatic production of cytotoxic cytokines and superoxide anions.
（1）先前接触脂多糖会诱导对随后短期酒精中毒肝脏效应的交叉耐受性；（2）短期酒精中毒使肝脏对内毒素血症的效应产生抗性，从而导致超氧化物和肿瘤坏死因子的产生减少。在第一组实验中，雄性Sprague-Dawley大鼠在静脉推注乙醇（1.75 g/kg）前48小时静脉注射大肠杆菌脂多糖（LPS）（0.5 mg/kg），随后以250 - 300 mg/kg/小时的速度持续3 - 5小时。在乙醇输注3小时后测量灌注肝脏中的超氧化物释放。LPS预处理减弱了灌注肝脏中乙醇介导的超氧化物阴离子释放。佛波酯肉豆蔻酸酯对肝脏超氧化物释放的刺激作用也降低了。在第二组实验中，先前用乙醇处理5小时的大鼠静脉注射LPS（1 mg/kg）。在注射LPS后90分钟，收集血清用于检测肿瘤坏死因子α。在注射LPS后3小时测定肝脏中超氧化物阴离子的释放。急性酒精中毒5小时显著降低了LPS诱导的血清肿瘤坏死因子活性以及灌注肝脏的自由基释放。LPS诱导的死亡率也降低了。在两组实验中，交叉耐受期间血清皮质类固醇水平均降低。这些结果表明，急性酒精中毒和内毒素血症之间形成了交叉耐受，表现为肝脏中细胞毒性细胞因子和超氧化物阴离子的产生减少。
