D-半乳糖胺／脂多糖所致小鼠急性肝衰竭模型正交试验优化研究  

Orthogonal design based optimization of a mouse model of acute fiver failure induced by D-galactosamine and fipopolysaccharide

作　　者：杨昊臻 陈珑 童晶晶 张慧英 逄菲 许执恒 辛绍杰[2] 胡瑾华 

机构地区：[1]解放军医学院,北京100853 [2]解放军第三O二医院肝衰竭诊疗与研究中心

出　　处：《中华肝脏病杂志》2013年第6期464-466,共3页Chinese Journal of Hepatology

基　　金：国家自然科学基金（81171641）

摘　　要：目的通过正交试验优化D-氨基半乳糖（D—GaIN）和脂多糖（LPS）致急性肝衰竭模型，确定合理造模剂量，以期使造模更加符合研究需要。方法选取3个可能影响造模成功率的指标为实验因素：D—GaIN剂量、LPS剂量、稀释倍数，每个实验因素选取4个水平，利用L16（45）正交表安排试验，以小鼠24h病死率为考察指标。观察小鼠血清ALT、肝组织学改变，肝脏细胞凋亡情况以验证造模效果。结果优化后理想造模给药方案为D—GaIN350mg／kg联合LPS30ug／kg，混合后稀释3倍，腹腔注射。造模后6h可出现典型肝衰竭表现。结论优化了D—GalN／LPs致小鼠ALF模型，使其更符合科研需要。Objective To apply an orthogonal design optimization strategy to a mouse model of acute liver failure induced by D-galactosamine （D-GaIN） and lipopolysaccharide （LPS） exposure. Methods A four-level orthogonal array design （L16（45）） was constructed to test factors with potential impact on successful establishment of the model （D-GaIN and LPS dosages, and dilution rate of the D-GaIN/ LPS mixture）. The mortality rate of mice within 24 hours of D-GalN/LPS administration was determined by the Kaplan-Meier method. The model outcome was verified by changes in serum alanine transferase level, liver histology, and hepatocyte apoptosis. Results The orthogonal array identified the optimal model technique as intraperitoneal injection of a combination of D-GaIN and LPS at dosages of 350 mg/kg and 30 μg/kg, respectively, and using a dilution rate of 3. The dosages tested had no effect on survival. The typical signs of liver failure appeared at 6 hrs after administration of the D-GalN/LPS combination. Conclusion The orthogonal design optimization strategy provided a procedure for establishing a mouse model of acute liver failure induced by D-GaIN and LPS that showed appropriate disease outcome and survival, and which will serve to improve future experimental research of acute liver failure.

关 键 词：肝功能衰竭 模型 动物 细胞凋亡 

分 类 号：R575.3[医药卫生—消化系统]