析因实验法建立规范化小鼠暴发性肝衰竭模型

Optimization of mouse model of fulminant hepatic failure by factorial experiment

目的:建立稳定有效的小鼠D-氨基半乳糖(D-GalN)和内毒素(LPS)致暴发性肝衰竭(FHF)模型．方法:采用析因实验法,选择两个影响模型成功率的因素:D-GalN和LPS的攻击剂量．两者各选取三个水平,以小鼠24 h病死率为评价指标,观察实验鼠的血清肝功能和肝组织病理学改变．结果:优选出两种较理想的给药方案:D-GalN 600 mg／kg联合LPS 0．5 mg／kg和D-GalN 800 mg／kg联合LPS 0．04 mg／kg腹腔注射．不同剂量的D-GalN和LPS对模型的病死率均有影响(F=36．878,P=0．000;F=32．386,P=0．000),均存在量效关系;而且D-GalN和LPS间存在交互作用(F=5．226,P=0．005),两种试剂合用可以明显提高模型的病死率．结论:建立了D-GalN和LPS致小鼠FHF的规范化模型．

AIM： To establish a stable and effective mouse model of fulminant hepatic failure （FHF） induced by D-galactosamine （D-GalN） and lipopolysaccharide （LPS）. METHODS： Two factors, attacking dosages of D-GalN and LP, influencing the success of modeling were chosen by factorial experiment. Three dosages of two factors were injected into the peritoneal cavity of mice and the death rate within 24 hours was calculated. Liver function and liver histopathological changes were also detected. RESULTS： Two administration projects were chosen： 600 mg/kg D-GalN combined with 0.5 mg/kg LPS, or 800 mg/kg D-GalN combined with 0.04 mg/kg LPS. The death rates were affected by D-GalN and LPS in dose-dependent manner （F = 36.878, P =0.000; F = 32.386, P = 0.000）. There are interaction between D-GalN and LPS （F = 5.226, P = 0.005）, and the combinatory administration of D-GalN and LPS increased the death rates of mice obviously. CONCLUSION： The standard model of mouse FHF can be established successfully using factorial experiment.