Dynamic Change Of Rabbit Acute Hepatic Failure Model Induced By Abdominal Injection Of D-galactosamine

Objective To develop an ideal rabbit model of acute hepatic failure by abdominal injection of D-Galactosamine and analyze the best dose and the best time of the replacement therapy (such as bone marrow stem cell transplantation)Methods Randomized blood samples of 15 healthy rabbits via the central artery were collected to examine the level of ALT,AST,ALB and TBIL.Then 55 healthy rabbits were randomly divided into 4 groups, of which were injected D-Galactosamine into abdominal cavity.A group: dosage 0.8 g/kg (n=10); B group:dosage 1.0 g/kg (n=15); C group: dosage 1.2g/kg (n=15); D group dosage 1.5g/kg (n=15).Reviewed clinical situation, liver function indexs and pathological changes about each group. Pathological specimens were obtained by continuously dynamic liver biopsy and immediately taking liver tissue through cutting the belly open after animal death.Observation time was 240h.Results1. Death rate comparision:The mortality in group B,C,D was higher than that of group A (P<0.05).The mortality in group D was higher than that of group B,C (p<0.05).The death rate comparison of group B and C was no statistically significance (p>0.05) 2. Changes of liver function indexs:At 12h, as compared with normal group, ALT and AST level in group B,C,D were higher (P<0.05), ALB and TBIL level were no differences (P>0.05); ALT and AST level in group C,D were higher than those in group B (P<0.05), but there were no different in ALB and TBIL level (P>0.05); All liver function indexs at 12h were no differences between group A and normal group (P>0.05)In group B, ALT and AST level at 24h,48h and 72h were respectively higher than those at 12h, ALB level at 24h,48h and 72h were respectively lower than those at 12h, TBIL level only 48h,72h were higher than 12h, that had no difference between 24h and 12h.And there were no differences among 24h,48h,72h liver function indexs level (compared with each other respectively, P>0.05)The animals died in the experimental observing time, there were no differences of ALT,AST and ALB level among all groups nearing death (p>0.05).At the same group ALT,AST and ALB level nearing death were significantly higher than those of 12h(p<0.05). TBIL level changed unsteadily.3. Histopathological changes:The liver histopathological changes of dead animals corresponded with the characteristics of AHF, and their pathological scores had no differences (p>0.05). There were differences in pathological scores after liver biopthe between A group and B group at 24h,72h,120h (p<0.05), but no differences between A group and B group at 240h. The rabbits in group B which would be developed AHF models, their liver histopathological changes approached or corresponded to the characteristics of AHF at 24h. At 72h, those changes presented more obviously.Conclusion To develop an ideal rabbit model of acute hepatic failure by abdominal injection of D-Galactosamine, the best dosage is 1.0g/kg, and the suitable time of the replacement therapy (such as bone marrow stem cell transplantation) is 24-72h after administration,24-48h is the best time.