Takada Y, Boudjema K, Jaeck D, Bel-Haouari M, Doghmi M, Chenard M P, Wolf P, Cinqualbre J
Laboratoire de Chirurgie Experimentale, Fondation Transplantation, Strasbourg, France.
Transplantation. 1995 Jan 15;59(1):10-6. doi: 10.1097/00007890-199501150-00003.
To investigate the role of platelet-activating factor (PAF) in the preservation/reperfusion injury of the liver graft, the effect of treatment with a potent PAF antagonist (E5880) was evaluated in a pig orthotopic liver transplantation model. The graft liver was flushed out and preserved for 8 hr at 4 degrees C using a simplified University of Wisconsin solution. The PAF antagonist was administered into the University of Wisconsin solution (1 mg/L), into the rinsing solution (1 mg/L), and to a recipient pig (0.3 mg/kg d.i.v.) in group 1. The PAF antagonist was not given in the control group (group 2). Postoperative survival of more than 12 hr was 100% (9/9) in group 1 and 56% (5/9) in group 2 (P < 0.05). At 12 hr after reperfusion of the graft (RPF), the arterial ketone body ratio (acetoacetate to 3-hydroxybutyrate) increased to 1.54 +/- 0.15 (mean +/- SEM) in group 1, compared with 0.95 +/- 0.09 (P < 0.05) in group 2. In group 2, blood leukocyte count decreased to 8.3 +/- 0.9 (x 10(3)/microliters) at 2 hr after RPF, in contrast to a slight increase in group 1 (14.3 +/- 1.8 x 10(3)/microliter, P < 0.01). At 4 hr after RPF, glutamic oxaloacetic transaminase (461 +/- 59 vs. 712 +/- 97 U/L, P < 0.05), glutamic pyruvic transaminase (65 +/- 4 vs. 82 +/- 5 U/L, P < 0.05), and the lactate level (6.2 +/- 1.1 vs. 9.4 +/- 1.0 mmol/L, P < 0.05) in arterial blood were significantly lower in group 1 than in group 2. Light and electron microscopic study at 1 hr after RPF showed neutrophil sludging in the sinusoids and sinusoidal endothelial cell damage in group 2, while these findings were attenuated in group 1. It is suggested that PAF plays a key role in microcirculatory disturbance of the liver graft manifested on reperfusion, and that the treatment with E5880 has a protective effect against preservation/reperfusion injury of the graft in liver transplantation.
为研究血小板活化因子（PAF）在肝移植保存/再灌注损伤中的作用，在猪原位肝移植模型中评估了强效PAF拮抗剂（E5880）治疗的效果。使用简化的威斯康星大学溶液将移植肝脏冲洗并在4℃保存8小时。在第1组中，将PAF拮抗剂加入威斯康星大学溶液（1mg/L）、冲洗液（1mg/L）中，并给予受体猪（0.3mg/kg静脉注射）。对照组（第2组）未给予PAF拮抗剂。第1组术后存活超过12小时的比例为100%（9/9），第2组为56%（5/9）（P<0.05）。在移植肝再灌注（RPF）后12小时，第1组动脉血酮体比值（乙酰乙酸与3-羟基丁酸）升至1.54±0.15（平均值±标准误），而第2组为0.95±0.09（P<0.05）。在第2组中，RPF后2小时血白细胞计数降至8.3±0.9（×10³/微升），而第1组略有升高（14.3±1.8×10³/微升，P<0.01）。RPF后4小时，第1组动脉血中的谷草转氨酶（461±59对712±97U/L，P<0.05）、谷丙转氨酶（65±4对82±5U/L，P<0.05）和乳酸水平（6.2±1.1对9.4±1.0mmol/L，P<0.05）均显著低于第2组。RPF后1小时的光镜和电镜研究显示，第2组肝血窦中有中性粒细胞淤滞和肝血窦内皮细胞损伤，而第1组这些表现有所减轻。提示PAF在再灌注时肝移植微循环紊乱中起关键作用，且E5880治疗对肝移植中移植物的保存/再灌注损伤具有保护作用。
