Ninomiya Mizuki, Shimada Mitsuo, Harada Noboru, Shiotani Satoko, Hiroshige Shoji, Soejima Yuji, Suehiro Taketoshi, Sugimachi Keizo
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. nnmym@ surg2.med.kyushu-u.ac.jp.
Transplantation. 2002 Nov 27;74(10):1470-2. doi: 10.1097/00007890-200211270-00021.
Despite growing evidence that reactive oxygen species are responsible for deleterious effects of ischemia-reperfusion (I/R) injury of the liver, there exists, until now, no reliable antioxidant therapeutics applicable in the clinical setting. We investigated the effects of free radical scavenger, 3-methyl-1-phenyl-2-pyrazolin-5-one (MCI-186), using an isolated liver perfusion model to elucidate its possible therapeutic effects on hepatic warm I/R injury. Isolated livers from Wistar rats were reperfused for 120 min with an oxygenated Krebs-Henseleit bicarbonate buffer after 1 hr of warm ischemia. Addition of MCI-186 (1 mg/L) into the perfusate significantly improved portal flow, hepatic enzyme release into the perfusate, total bile production, histologic alteration, and malondialdehyde concentration but not sinusoidal endothelial cell function as assessed by the clearance of hyaluronic acid. MCI-186 seems to have protective effects against hepatic warm I/R injury by attenuating the damage of the hepatocyte, which is the major target of oxidative damage in this model.
尽管越来越多的证据表明活性氧是肝脏缺血再灌注（I/R）损伤产生有害影响的原因，但迄今为止，尚无适用于临床的可靠抗氧化治疗方法。我们使用离体肝脏灌注模型研究了自由基清除剂3-甲基-1-苯基-2-吡唑啉-5-酮（MCI-186）的作用，以阐明其对肝脏热I/R损伤可能的治疗效果。Wistar大鼠的离体肝脏在热缺血1小时后，用含氧的Krebs-Henseleit碳酸氢盐缓冲液再灌注120分钟。向灌注液中添加MCI-186（1mg/L）可显著改善门静脉血流、灌注液中肝酶的释放、总胆汁生成、组织学改变和丙二醛浓度，但通过透明质酸清除率评估的肝窦内皮细胞功能未得到改善。MCI-186似乎通过减轻肝细胞损伤而对肝脏热I/R损伤具有保护作用，肝细胞是该模型中氧化损伤的主要靶点。
