Bautista Abraham P
Department of Physiology and National Institute on Alcohol Abuse and Alcoholism-Sponsored Alcohol Research Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA.
Antioxid Redox Signal. 2002 Oct;4(5):721-31. doi: 10.1089/152308602760598864.
This work tests the hypothesis that withdrawal from an acute ethanol binge regulates the production of reactive oxygen species (ROS) and chemokines by Kupffer cells, and as a result compromises or protects the liver from injury. Male Sprague-Dawley rats received an intravenous ethanol bolus (1.75 g/kg), followed by an intravenous infusion of 200-300 mg/kg/h for 12 h. At 12 h, ethanol infusion was stopped and replaced by saline. At 18 h, rats were subjected to 45 min of partial hepatic ischemia, followed by 0-24 h of reperfusion (I/R). At specific time points, Kupffer cells were isolated for superoxide anion assay and CINC (cytokine-induced neutrophil chemoattractant) and MIP-2 (macrophage inflammatory protein-2) production in vitro. Alanine transferase (ALT) activity, endotoxin, CINC, and MIP-2 were measured in serum samples taken at appropriate intervals. Results show that at 3 h post reperfusion, serum ALT was significantly elevated in the ethanol-treated group + I/R, compared with the saline + I/R group. ROS production by Kupffer cells at this time was also significantly increased compared with the saline + I/R group. However, ethanol withdrawal + I/R did not significantly alter CINC and MIP-2 production at 3 h of reperfusion. After 24 h, serum ALT was lower in the ethanol + I/R group than in the saline + I/R group. Superoxide anion and MIP-2 releases by Kupffer cells were not statistically significantly different between these two groups at this time. CINC production by Kupffer cells from the ethanol-treated + I/R group was significantly lower than in the saline + I/R group. Concomitantly, CINC and nuclear factor-kappaB (NF-kappaB) mRNAs and NF-kappaB translocation and binding in Kupffer cells in this treatment group were down-regulated. Moreover, the number of polymorphonuclear neutrophils (PMNs) sequestered in the liver was significantly lower in the ethanol + I/R group than in the saline-treated group. ROS and chemokine productions in sham animals with or without ethanol were lower than in the I/R group. These data suggest that acute ethanol binge followed by withdrawal may compromise the liver to injury during the early phase, whereas in the later phase it may be protective. Furthermore, these results support the notion that Kupffer cells are involved in hepatic injury in the early phase, whereas PMNs participate more actively during the later phase of reperfusion.
急性乙醇暴饮后戒断会调节库普弗细胞中活性氧（ROS）和趋化因子的产生，进而影响肝脏损伤，可能导致肝脏受损或起到保护作用。雄性Sprague-Dawley大鼠静脉注射一次乙醇推注量（1.75 g/kg），随后以200 - 300 mg/kg/h的速度静脉输注12小时。12小时后，停止乙醇输注，改为输注生理盐水。18小时时，对大鼠进行45分钟的部分肝脏缺血处理，随后进行0 - 24小时的再灌注（I/R）。在特定时间点，分离库普弗细胞用于体外超氧阴离子检测以及CINC（细胞因子诱导的中性粒细胞趋化因子）和MIP-2（巨噬细胞炎性蛋白-2）产生的检测。在适当的时间间隔采集血清样本，检测丙氨酸转氨酶（ALT）活性、内毒素、CINC和MIP-2。结果显示，再灌注3小时时，乙醇处理组 + I/R的血清ALT显著高于生理盐水 + I/R组。此时，与生理盐水 + I/R组相比，库普弗细胞产生的ROS也显著增加。然而，乙醇戒断 + I/R在再灌注3小时时并未显著改变CINC和MIP-2的产生。24小时后，乙醇 + I/R组的血清ALT低于生理盐水 + I/R组。此时，这两组库普弗细胞释放的超氧阴离子和MIP-2在统计学上无显著差异。乙醇处理 + I/R组库普弗细胞产生的CINC显著低于生理盐水 + I/R组。同时，该处理组库普弗细胞中CINC和核因子-κB（NF-κB）mRNA以及NF-κB的易位和结合均下调。此外，乙醇 + I/R组肝脏中多形核中性粒细胞（PMN）的滞留数量显著低于生理盐水处理组。有或无乙醇处理的假手术动物的ROS和趋化因子产生均低于I/R组。这些数据表明，急性乙醇暴饮后戒断在早期可能使肝脏易受损伤，而在后期可能具有保护作用。此外，这些结果支持以下观点：库普弗细胞在早期参与肝脏损伤，而PMN在再灌注后期更活跃地参与其中。
