药物性急性肝衰竭动物模型的建立

Establishment of pig models of acute hepatic failure induced by drugs

目的建立用于人工肝实验研究的急性肝衰竭大动物模型。方法应用中国实验小型猪13头随机分为3组,低剂量组(n=3)给予1.0g/kg的D-氨基半乳糖;中剂量组(n=6)给予1.2g/kg的药物;大剂量组(n=4)给药剂量为1.5g/kg。观察比较每组动物的一般状况、生存时间、生理生化指标、颅内压、组织病理等方面的变化,从中得出建立急性肝衰竭动物模型的较稳定方法。结果低剂量组动物在给药后均出现一过性的肝功能损害,未出现肝昏迷表现,在给药后3～4d肝功能开始恢复,约1周后指标基本恢复正常,所有动物均存活;高剂量组的动物肝损害出现时间早,损伤剧烈,存活时间短(24.8±5.3h),均死于严重的肝衰竭。中等剂量组的动物在给药后12h各项指标开始变化明显,在给药48h时损伤达高峰,存活时间为67.9±9.4h,最终死于严重的肝衰竭。结论应用药物方法能建立急性肝衰竭动物模型,其中D-氨基半乳糖1.2g/kg的给药剂量建立的模型稳定性好,且能较好模拟临床急性肝衰竭发生、发展的病理、生理过程,可作为人工肝治疗的实验平台。

Objective To establish a large animal model of acute hepatic failure for assessing bioartificial liver support system. Methods Thirteen minipigs were randomly assigned to 3 groups, in which acute hepatic failure was induced by the administration of D-galactosamine in the dosage of 1.0 g/kg, 1.2 g/kg and 1.5 g/kg, respectively. By observing and comparing the general state, survival time, biochemical indexes, and the changes in intracranial pressure and histopathology, a method of establishing a stable animal model of acute hepatic failure was found. Results In low-dosage group, there was a temporary hepatic injury, but no hepatic coma Liver function became normal 3 to 4 days after the administration and various indexes normal after a week or so. All the animals survived. In the high-dosage group, hepatic injury occurred early and severely. All the animals died of severe hepatic failure with a survival time of 24.8± 5.3 hours. In the medium-dosage group, various indexes changed obviously 12 hours after the administration and hepatic injury reached its peak after 48 hours. All the animals died of severe hepatic failure with a survival time of 67.9 ± 9.4 hours. Conclusion By administering D-galactosamine to induce acute hepatic failure, animal models can be established. The one induced by 1.2 g/kg of D-galactosamine is more stable and can demonstrate the pathophysiologic changes in the progression of acute hepatic failure, so it can serve as an experimentalmodel for assessing artificial liver support system.