Establishment of a mouse model of acute liver failure induced by LPS/D-GalN
10.3969/j.issn.1005-4847.2014.03.003
- VernacularTitle:LPS/D-GalN 诱导小鼠急性肝损伤模型的建立
- Author:
Xiaohong WU
;
Yan GUO
;
Chenfeng LIU
;
Tongtong GAO
;
Hong YU
;
Shihui SUN
;
Yusen ZHOU
- Publication Type:Journal Article
- Keywords:
Lipopolysaccharide,LPS;
D-galactosamine,D-GalN;
Acute liver failure;
Inflammation;
Mouse
- From:
Acta Laboratorium Animalis Scientia Sinica
2014;(3):15-19
- CountryChina
- Language:Chinese
-
Abstract:
Objective To establish a mouse model of acute liver failure induced by lipopolysaccharide /D-galac-tosamine ( LPS/D-GalN) .Methods The optimum dose of LPS/D-GalN was determined by i .p.injection of eight differ-ent doses of LPS and D-GalN into 40 female C57BL/6 mice and observation of their survival time .Then, 32 female C57BL/6 mice were i.p.injected with the optimal dose of LPS/D-GalN and sacrificed at 0, 1, 4, 8 hours after the injec-tion, 8 mice in each group.The control mice received saline injection .Hepatic changes were observed by pathology and se-rum ALT, IL-6, MCP-1 and TNF-αwere measured by biochemistry or flow cytometry .Results LPS (2.5 mg/kg) and D-GalN (0.3 g/kg) were determined as the optimal dose for the establishment of mouse model of acute liver injury .Com-pared with the control group , the hepatocellular damages were progressing in a positive correlation with the time course after LPS/D-GalN administration .The level of serum ALT was significantly increased after LPS/D-GalN administration ( P <0.001).The levels of inflammatory cytokines IL-6, MCP-1 and TNF-αwere increased and reached a peak at one hour after LPS/D-GalN administration and then decreased almost to that of the control group 8 hours later(P<0.001).Conclusions The mouse model of acute liver injury is successfully established by LPS /D-GalN administration , and provide an effective animal model for the study of pathogenic mechanisms of acute liver failure and evaluation of therapeutic drugs .