中国实验动物学报2026，Vol.34Issue(7)：937-948,12.DOI:10.3969/j.issn.1005-4847.2026.07.001
6种精准脂肪肝小鼠模型病理表型与免疫特征的比较分析
Comparison of pathological phenotypes and immune characteristics in six precision mouse models of fatty liver disease
摘要
Abstract
Objective To compare the effects of six common diet-induced modeling method on mouse models of fatty liver disease,and to further explore the pathological mechanisms through precision modeling.Methods Four-week-old male C57BL/6J mice were randomly divided into 7 groups:normal diet(ND),high-fat diet(HFD),high-fat and high-sugar diet(HFHSD),choline-deficient amino acid diet(CDAA),amylin liver NASH diet(AMLN),carbon tetrachloride(CCl4)treatment,and alcoholic liquid diet(AFLD)groups(n=6～8),among which the latter six were designated as modeling groups.The modeling period lasted for 16 weeks.Multi-dimensional analyses,including serum biochemistry,liver histology,and immunology,were performed to evaluate the pathological phenotypes and immune characteristics of each experimental model.Results Compared with the ND group,(1)The body mass,liver mass,and liver index of mice in the HFD,HFHSD,CDAA and AMLN groups increased significantly(P＜0.001);except for the CCl4 group,the hepatic triglyceride(TG)content and epididymal fat mass of mice in other groups increased significantly(P＜0.05).(2)The serum TG and total cholesterol levels of mice in all modeling groups increased significantly(P＜0.001).(3)Serum levels of interleukin-1(IL-1),IL-6,IL-8 and TNF-α in all modeling groups increased significantly(P＜0.05).(4)Pathological analysis showed that a large number of lipid droplets formed in the livers of mice in all groups except the CCl4 group;inflammatory cell infiltration was observed in the livers of mice in the AMLN,AFLD,and CCl4 groups,with obvious liver fibrosis observed in the CCl4 group.(5)The number of CD4 and CD8-positive cells in the livers of mice in all groups except the CCl4 group increased;CD19-positive cells were concentrated in the HFHSD and AMLN groups,while F4/80-positive cells were concentrated in the AMLN and CCl4 groups.Conclusions HFD,HFHSD and CDAA diets were deemed suitable for metabolic dysfunction-associated steatotic liver disease,while the AMLN diet was focused on the exploration of metabolic dysfunction-associated steatohepatitis,and liver fibrosis mechanisms.The CCl4 model can be used for liver fibrosis and related research,while the Lieber-DeCarli alcoholic liquid diet is ideal for studying alcoholic fatty liver disease.关键词
脂肪肝/C57BL/6J小鼠/精准建模/病理表型/免疫特征Key words
fatty liver disease/C57BL/6J mice/precision modeling/pathological phenotype/immune characteristic分类
生物科学引用本文复制引用
栗宏伟,章慕宬,高静,许涛,周燕蓉,陈侃..6种精准脂肪肝小鼠模型病理表型与免疫特征的比较分析[J].中国实验动物学报,2026,34(7):937-948,12.基金项目
国家自然科学基金项目(81972281),国家级大学生创新创业训练计划(202410338074). Funded by National Natural Science Foundation of China(81972281),National College Students'Innovation and Entrepreneurship Training Program(202410338074). （81972281）
