脂多糖联合D-氨基半乳糖诱导急性重症肝炎小鼠模型的建立

Establishment of Acute Fulminant Hepatitis Mouse Model Induced by Lipopolysaccharide and D-galactosamine

目的:建立存活时间较长的急性重症肝炎小鼠模型。方法:将50只BALB/c小鼠平均分成5组,其中A、B、C、D 4组为实验组,E组为对照组;实验组分别给予D-氨基半乳糖(D-GalN)和脂多糖(LPS),剂量分别为800 mg/kg和10μg/kg、500 mg/kg和10μg/kg、500 mg/kg和5μg/kg3、00 mg/kg和5μg/kg,用生理盐水稀释至1 mL,行腹腔注射;对照组E腹腔注射生理盐水2 mL。以12 h死亡率、24 h死亡率及肝组织学改变为观察指标。结果:A、B、C、D及E组小鼠12 h死亡率分别为80%%、30%、10%、0和0;24 h死亡率分别为90%、60%、30%、0和0;A和B组小鼠肝组织学均呈急性重症肝炎表现,C组中有5只小鼠肝组织学符合重症肝炎的表现,而该组其余小鼠及D组所有肝组织学虽有炎症改变,但达不到重症肝炎的程度,E组肝组织学表现正常。结论:LPS 10μg/kg联合D-Gal N500 mg/kg可成功建立12 h存活率较高的急性重症肝炎小鼠模型。

Objective：To establish an acute fulminant hepatitis mouse model with longer survival time. Methods： Fifty mice were equably divided into 5 groups. Groups A, B, C and D were experimental groups, and the doses of D-galactosamine （D-GaIN） and lipopolysaccharide（LPS） for the groups were as follows ： 800 mg/kg and 10μg/kg, 500 mg/kg and 10μg/kg, 500 mg/kg and 5 μg/kg, 300 mg/kg and 5μg/kg, respectively. All the reagents were dissolved by normal saline and stored in Ep tubes with a total volume of 1 mL,given by intraperitoneal injection. The mice in control group were given 1 mL normal saline by intraperitoneal injection. Liver histological changes, the 12-hour death rate and 24 hour death rate were observed. Results： The 12-hour death rate of group A, B, C, D and E was 80 %, 30 %, 10 %, 0 and 0 respectively, and the 24-hour death rate was 90 %, 60 % , 30 % , 0 and 0 respectively. The liv- er histology of groups A and B manifested as acute fulminant hepatitis,groups C and D manifested as inflammation and necrosis in different degree,while liver histology of group D was normal. Conclusion：The acute fulminant hepati- tis mouse model with longer survival time could be successfully induced by the combination of LPS 10 μg/kg and D-GaIN 500 mg/kg.