中国实验动物学报2025，Vol.33Issue(1)：34-43,10.DOI:10.3969/j.issn.1005-4847.2025.01.004
三种非酒精性脂肪肝炎模型病证特点的比较研究
Comparison research of disease characteristics in three non-alcohol steatohepatitis models
摘要
Abstract
Objective To compare the serological and pathological characteristics of 3 nonalcoholic steatohepatitis(NASH)models:high-fat diet(HFD)with carbon tetrachloride(CCl4)injection,methionine and choline deficient diet(MCD),and Aymlin liver NASH(AMLN)diet-induced NASH models.Methods 3 NASH models were established by feeding mice an HFD with CCl4 injection for 10 weeks,MCD for 8 weeks and NASH for 26 weeks.After feeding,serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),glucose(GLU),liver triglyceride(TG),total cholesterol(TC),and malondialdehyde(MDA)levels and superoxide dismutase(SOD)activity were measured.Insulin levels were measured by enzyme-linked immunosorbent assay(ELISA)and the homeostasis model assessment of insulin resistant(HOMA-IR)index was calculated.Hematoxylin-eosin(HE),Sirius red,and oil red staining were used to indicate pathological changes to the liver.The NAS score was used to grade the pathology.Results Compared to each normal control(NC)group mice,all mice in the 3 model groups had an obvious increase in serum transaminase and liver TG,TC,MDA levels and SOD activity.The levels of serum FINS,GLU and the HOMA-IR index were significantly increased in the AMLN and CCl4+HFD model groups but decreased in the MCD model group.According to the HE,oil red staining and NAS score,mice in all 3 groups had NASH phenotypic changes.Liver collagen deposition was most obvious in mice in theCCl4+HFD model group.Liver lipid droplets were most abundant in the AMLN model group.Conclusions All the above 3 animal models can stably simulate the serological and pathological changes of NASH in human.The AMLN model can simulate the progress and mechanism of the disease,as well as systemic metabolic disorders such as insulin resistance and oxidative stress.However,it is time-consuming and the fibrosis progression rate is slow.The MCD diet can simulate the serological and pathological features of NASH in 8 weeks,but no obesity or insulin resistance occurred.The CCl4 combined with HFD model can induce NASH model in 10 weeks,which can simulate its serological and pathological changes,and the liver has obvious fibrous deposition and oxidative stress damage.关键词
非酒精性脂肪肝炎/MCD模型/AMLN模型/胰岛素抵抗Key words
non-alcoholic steatohepatitis/MCD model/amylin model/insulin resistance分类
生物学引用本文复制引用
薛静波,杨金凤,黄恺,彭渊,陶艳艳,刘成海..三种非酒精性脂肪肝炎模型病证特点的比较研究[J].中国实验动物学报,2025,33(1):34-43,10.基金项目
国家自然科学基金面上项目(82274305),上海市临床重点专科建设项目(shslczdzk01201).Funded by National Natural Science Foundation of China(82274305),Shanghai Key Clinical Specialty of Traditional Chinese Medicine(shslczdzk0 1201). （82274305）
