Fulminant liver failure models with subsequent encephalopathy in the mouse  

作　　者：Ann-Marie T Baine Tomohide Hori Lindsay B Gardner Shinji Uemoto Justin H Nguyen 

机构地区：[1]Department of Neuroscience Mayo Clinic in Florida,Jacksonville,FL 32224,USA [2]Divisions of Hepato-Pancreato-Biliary,Transplant and Pediatric Surgery,Department of Surgery,Kyoto University Graduate School of Medicine,Kyoto 606-8507,Japan [3]Division of Transplant Surgery,Department of Transplantation,Mayo Clinic in Florida,Jacksonville,FL 32224,USA

出　　处：《Hepatobiliary & Pancreatic Diseases International》2011年第6期611-619,共9页国际肝胆胰疾病杂志（英文版）

基　　金：supported by grants from the Deason Foundation (Sandra and Eugene Davenport,Mayo ClinicCD CRT-II);the AHA (0655589B);the NIH (R01NS05164601A2);the Uehara Memorial Foundation (200940051)

摘　　要：BACKGROUND:A reliable model of fulminant liver failure (FLF) is urgently required in this research field.This study aimed to develop a murine FLF model.METHODS:We used three groups of male C57BL/6 mice:control,with azoxymethane treatment (AOM group),and with galactosamine and tumor necrosis factor-alpha treatment (Gal+TNF-α group).The effects of body temperature (BT) control on survival in all three groups were investigated Using BT control,we compared the survival,histopathological findings and biochemical/coagulation profiles between the two experimental groups.The effects of hydration on international normalized ratios of prothrombin time (PT INRs) were also checked.Dose-dependent survival curves were constructed for both experimental groups.Neurological behavior was assessed using a coma scale.RESULTS:No unexpected BT effects were seen in the control group.The AOM group,but not the Gal+TNF-α group showed a significant difference in survival curves between those with and without BT care.Histopathological assessment showed consistent FLF findings in both experimental groups with BT care.There were significant differences between the experimental groups in aspartate aminotransferase levels and PT-INRs,and significant differences in PT-INRs between the sufficiently and insufficiently hydrated groups.There were significant differences between FLF models in the duration of each coma stage,with significant differences in stages 1 and 3 as percentages of the disease state (stages 1-4).The two FLF models with BT care showed different survival curves in the dose-dependent survival study.CONCLUSIONS:AOM provides a good FLF model,but requires a specialized environment and careful BT control.Other FLF models may also be useful,depending on the research purpose.Thoughtful attention to caregiving and close observation are indispensable for successful FLF models.BACKGROUND:A reliable model of fulminant liver failure (FLF) is urgently required in this research field.This study aimed to develop a murine FLF model.METHODS:We used three groups of male C57BL/6 mice:control,with azoxymethane treatment (AOM group),and with galactosamine and tumor necrosis factor-alpha treatment (Gal+TNF-α group).The effects of body temperature (BT) control on survival in all three groups were investigated Using BT control,we compared the survival,histopathological findings and biochemical/coagulation profiles between the two experimental groups.The effects of hydration on international normalized ratios of prothrombin time (PT INRs) were also checked.Dose-dependent survival curves were constructed for both experimental groups.Neurological behavior was assessed using a coma scale.RESULTS:No unexpected BT effects were seen in the control group.The AOM group,but not the Gal+TNF-α group showed a significant difference in survival curves between those with and without BT care.Histopathological assessment showed consistent FLF findings in both experimental groups with BT care.There were significant differences between the experimental groups in aspartate aminotransferase levels and PT-INRs,and significant differences in PT-INRs between the sufficiently and insufficiently hydrated groups.There were significant differences between FLF models in the duration of each coma stage,with significant differences in stages 1 and 3 as percentages of the disease state (stages 1-4).The two FLF models with BT care showed different survival curves in the dose-dependent survival study.CONCLUSIONS:AOM provides a good FLF model,but requires a specialized environment and careful BT control.Other FLF models may also be useful,depending on the research purpose.Thoughtful attention to caregiving and close observation are indispensable for successful FLF models.

关 键 词：animal model acute liver failure AZOXYMETHANE GALACTOSAMINE tumor necrosis factor-alpha 

分 类 号：R575.3[医药卫生—消化系统]