Bautista A P, Spitzer J J
Department of Physiology and Alcohol Research Center, Louisiana State University Medical Center, New Orleans 70112, USA.
Alcohol Clin Exp Res. 1996 May;20(3):502-9. doi: 10.1111/j.1530-0277.1996.tb01083.x.
The present studies were performed to test the hypothesis that Kupffer and endothelial cells are activated after recovery from an acute alcohol binge, which is accompanied by formation of oxygen-derived radicals. These radicals have been implicated in the pathogenesis of alcohol-mediated tissue injury in a number of organs. Male Sprague-Dawley rats received an intravenous injection of 20% ethanol in saline (1.75 g/kg), followed by an intravenous infusion (250 to 300 mg/kg/hr) for 12 hr. At the end of 12-hr infusion, ethanol was replaced by saline, and the infusion was continued for a further 6 hr. This was referred to as the recovery period. The 6-hr recovery period was selected because superoxide anion generation by the perfused liver peaked at this time point. Superoxide anion formation by the perfused liver was measured by the superoxide dismutase-inhibitable reduction of ferricytochrome c. Kupffer and endothelial cells were isolated for the determination of in vivo glucose uptake and in vitro superoxide anion release. Results show that a significant (p < 0.05) amount of superoxide (1.54 nmol/min/g) was generated by the perfused liver at 6 hr recovery after 12 hr of ethanol infusion. Serum ALT activity was also elevated in this treatment group. Time-matched control-saline infused animals or ethanol-treated animals without a recovery period released < 0.2 nmol/min/g of superoxide. The postrecovery superoxide production and an accompanying increase in the in vivo glucose uptake were also observed in isolated Kupffer and endothelial cells. Depletion of Kupffer cells by gadolinium chloride before ethanol treatment and recovery was associated with significant attenuation of free radical formation by the perfused liver and reduction of serum ALT. These studies demonstrate that recovery from an acute alcohol binge has a stimulating effect on hepatic sinusoidal superoxide production, and it may also affect liver function.
在急性酒精狂饮恢复后，库普弗细胞和内皮细胞会被激活，同时伴有氧衍生自由基的形成。这些自由基与多种器官中酒精介导的组织损伤的发病机制有关。雄性Sprague-Dawley大鼠静脉注射20%乙醇生理盐水溶液（1.75 g/kg），随后静脉输注（250至300 mg/kg/小时）12小时。在12小时输注结束时，用生理盐水替代乙醇，并继续输注6小时。这被称为恢复期。选择6小时的恢复期是因为灌注肝脏产生超氧阴离子在这个时间点达到峰值。通过超氧化物歧化酶抑制的细胞色素c铁还原法测量灌注肝脏中超氧阴离子的形成。分离库普弗细胞和内皮细胞以测定体内葡萄糖摄取和体外超氧阴离子释放。结果显示，在乙醇输注12小时后的6小时恢复期，灌注肝脏产生了显著（p < 0.05）量的超氧阴离子（1.54 nmol/分钟/克）。该治疗组血清ALT活性也升高。时间匹配的输注生理盐水的对照动物或未经过恢复期的乙醇处理动物释放的超氧阴离子<0.2 nmol/分钟/克。在分离的库普弗细胞和内皮细胞中也观察到恢复期后超氧阴离子的产生以及体内葡萄糖摄取的相应增加。在乙醇处理和恢复前用氯化钆耗尽库普弗细胞与灌注肝脏自由基形成的显著减弱和血清ALT的降低有关。这些研究表明，急性酒精狂饮后的恢复对肝窦超氧阴离子的产生有刺激作用，并且可能也会影响肝功能。
