Zhou P, Xia J, Guo G, Huang ZX, Lu Q, Li L, Li HX, Shi YJ, Bu H. A Macaca mulatta model of fulminant hepatic failure. World J Gastroenterol 2012; 18(5): 435-444 [PMID: 22346249 DOI: 10.3748/wjg.v18.i5.435]
Corresponding Author of This Article
Yu-Jun Shi, MD, PhD, Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, West China Hospital, Sichuan University, No. 1 Keyuan 4th Road, Chengdu 610041, Sichuan Province, China. shiyujun@scu.edu.cn
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World J Gastroenterol. Feb 7, 2012; 18(5): 435-444 Published online Feb 7, 2012. doi: 10.3748/wjg.v18.i5.435
A Macaca mulatta model of fulminant hepatic failure
Ping Zhou, Jie Xia, Gang Guo, Zi-Xing Huang, Qiang Lu, Li Li, Hong-Xia Li, Yu-Jun Shi, Hong Bu
Ping Zhou, Hong Bu, Department of Pathology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
Jie Xia, Gang Guo, Li Li, Yu-Jun Shi, Hong Bu, Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
Zi-Xing Huang, Department of Radiology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
Qiang Lu, Department of Ultrasound, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
Hong-Xia Li, The National Chengdu Center for Safety Evaluation of Drugs, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
Author contributions: Zhou P, Shi YJ and Bu H designed the project; Zhou P, Xia J, Guo G and Shi YJ performed the experiments; Zhou P and Shi YJ contributed to the discussion of the data and wrote the manuscript; Huang ZX contributed to the MRI examination; Lu Q contributed to the ultrasound examination; Li L contributed to the production and staining of section; Li HX provided the experimental animals and contributed to the biochemical examination.
Supported by National Basic Research Program of China, No. 2009CB522401; and grand from Natural Science Foundation of China, No. 30870983 and 30971118
Correspondence to: Yu-Jun Shi, MD, PhD, Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, West China Hospital, Sichuan University, No. 1 Keyuan 4th Road, Chengdu 610041, Sichuan Province, China. shiyujun@scu.edu.cn
Telephone: +86-28-85164030 Fax: +86-28-85164034
Received: May 19, 2011 Revised: June 23, 2011 Accepted: June 30, 2011 Published online: February 7, 2012
Abstract
AIM: To establish an appropriate primate model of fulminant hepatic failure (FHF).
METHODS: 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.
RESULTS: 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.
CONCLUSION: 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.
