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| Establishment of a mouse model of acute liver failure induced by LPS/D-GalN |
| Received:January 21, 2014 |
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| DOI：10.3969/j.issn.1005-4847.2014.03.003 |
| KeyWord:Lipopolysaccharide, LPS;D-galactosamine, D-GalN;Acute liver failure;Inflammation;Mouse |
| Author | Institution |
| 吴小红 |
病原微生物生物安全国家重点实验室, 北京微生物流行病研究所, 北京 |
| 郭彦 |
病原微生物生物安全国家重点实验室, 北京微生物流行病研究所, 北京 |
| 刘晨风 |
病原微生物生物安全国家重点实验室, 北京微生物流行病研究所, 北京 ;安徽医科大学北京微生物流行病研究所, 合肥 |
| 高同同 |
病原微生物生物安全国家重点实验室, 北京微生物流行病研究所, 北京 |
| 于虹 |
病原微生物生物安全国家重点实验室, 北京微生物流行病研究所, 北京 |
| 孙世惠 |
病原微生物生物安全国家重点实验室, 北京微生物流行病研究所, 北京 |
| 周育森 |
病原微生物生物安全国家重点实验室, 北京微生物流行病研究所, 北京 |
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| Abstract: |
| Objective To establish a mouse model of acute liver failure induced by lipopolysaccharide/D-galactosamine (LPS/D-GalN). Methods The optimum dose of LPS/D-GalN was determined by i.p. injection of eight different 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 injection, 8 mice in each group. The control mice received saline injection. Hepatic changes were observed by pathology and serum ALT, IL-6, MCP-1 and TNF-α were 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. Compared 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-α were 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. |
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