Department of Pathology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China.
World J Gastroenterol. 2012 Feb 7;18(5):435-44. doi: 10.3748/wjg.v18.i5.435.
To establish an appropriate primate model of fulminant hepatic failure (FHF).
We have, for the first time, established a large animal model of FHF in Macaca mulatta by intraperitoneal infusion of amatoxin and endotoxin. Clinical features, biochemical indexes, histopathology and iconography were examined to dynamically investigate the progress and outcome of the animal model.
Our results showed that the enzymes and serum bilirubin were markedly increased and the enzyme-bilirubin segregation emerged 36 h after toxin administration. Coagulation activity was significantly decreased. Gradually deteriorated parenchymal abnormality was detected by magnetic resonance imaging (MRI) and ultrasonography at 48 h. The liver biopsy showed marked hepatocyte steatosis and massive parenchymal necrosis at 36 h and 49 h, respectively. The autopsy showed typical yellow atrophy of the liver. Hepatic encephalopathy of the models was also confirmed by hepatic coma, MRI and pathological changes of cerebral edema. The lethal effects of the extrahepatic organ dysfunction were ruled out by their biochemical indices, imaging and histopathology.
We have established an appropriate large primate model of FHF, which is closely similar to clinic cases, and can be used for investigation of the mechanism of FHF and for evaluation of potential medical therapies.
建立一种合适的暴发性肝衰竭（FHF）灵长类动物模型。
我们首次通过腹腔内注射毒蕈碱和内毒素在猕猴中建立了 FHF 的大型动物模型。通过临床特征、生化指标、组织病理学和影像学来动态研究动物模型的进展和结果。
我们的结果表明，酶和血清胆红素显著增加，毒素给药后 36 小时出现酶-胆红素分离。凝血活性明显降低。磁共振成像（MRI）和超声检查在 48 小时时逐渐显示出进行性恶化的实质异常。肝活检显示 36 小时和 49 小时分别出现明显的肝细胞脂肪变性和大量实质坏死。尸检显示肝脏典型的黄色萎缩。肝性脑病也通过肝昏迷、MRI 和脑水肿的病理变化得到证实。通过生化指标、影像学和组织病理学排除了肝外器官功能障碍的致死作用。
我们建立了一种合适的大型灵长类 FHF 模型，与临床病例非常相似，可用于研究 FHF 的发病机制和评估潜在的治疗方法。
