急性肝功能哀竭动物模型的建立

Establishment of an acute hepatic failure model in pigs

目的 建立与临床较相近的急性肝功能衰竭动物模型。方法 应用中国实验小型猪7头，采用Ⅰ期门静脉．下腔静脉吻合、Ⅱ期（48h后）供肝动脉暂时结扎4h的方法建立缺血性急性肝功能衰竭动物模型；中国实验小型猪6头给于1．2g／kg的D-氨基半乳糖诱导肝功能衰竭，建立药物性急性肝功能衰竭动物模型。观察比较每组动物一般状况、生存时间、生理生化指标、颅内压、组织病理等方面的变化。结果 在缺血性模型中，1头猪死于术中大出血，1头猪的生存时间超过5d，其余5头存活时间为18～30h[平均存活时间（22．5±5．6）h]；反映肝功能的主要指标（AST，总胆红素、凝血酶原时间、血氨、血糖）均明显异常；组织病理显示肝脏大块坏死。在药物性模型中，动物在给药后12h各项指标开始变化明显，给药后48h损伤达高峰，平均存活时间为（67．9±9．4）h，最终死于严重肝功能衰竭。结论应用缺血方法与药物方法均能建立急性肝功能衰谒动物模型，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功能衰竭发生发展的病理生理过程，可用于研究机制和评价疗效。

Objective To estabilish a large animal model for the study of acute hepatic failure. Methods We developed hepatic failure by two methods. （1） Surgical moldel of hepatic failure： Under general anesthesia, an end-to-side portocaval shunt was performed in seven trial minipigs. Forty-eight hours later after operation, these minipigs underwent transient total liver ischemia for 4 hours by ligating the hepatoduodenal ligament. （ 2 ） Chemical model of hepatic failure. Six minipigs were induced acute hepatic failure by administration of D-galactosamine in a dosage of 1.2 g/kg. Clinical data were recorded and blood for laboratory determinations were drawn at definite intervals, liver tissues were sampled for pathological examination. Results （ 1 ） In the surgical group, one pig died of bleeding, one animal survived more than 5 days, the other 5 pigs died with hepatic fialure （mean survival time was 22.5 ± 5.6 hours）, the biochemical indexes about liver functions were abnormal significantly. （2） In the drug-model, all animals died with in 80 hs after injection of galactosamine, resulting from acute hepatic failure characterized by marked increase in serum total bilirubin, liver enzymes, intracranial pressure and ammonia. Liver histology showed massive hepatoceUular necrosis in all six minipigs. Conclusion （ 1 ） Both methods of surgical and drug could induce acute hepatic failure, but the galactosamine model with dosage of 1.2 g/kg was more stable and reproducible, and appeared to be a better animal model for studying mechanism of AHF or evaluating therapeutic effect.