关键词: ob / ob 小鼠, 非酒精性脂肪肝, 动物模型

Abstract: Objective To compare the characteristics of several modeling method and to find an optimal model for non-alcoholic fatty liver disease on the basis of ob / ob mice. Method Firstly, the second and third exons of leptin gene were knocked out in the background of C57 mice to obtain leptin knockout mice (B-ob / ob mice) , and then HFMCD induction, WD induction, WD combined with carbon tetrachloride induction were performed on the basis of B-ob / ob mice. The levels of ALT, AST, triglyceride and cholesterol in the serum of the mice were analyzed under these induction method; the NAS score of NAFLD was assessed by pathological HE staining; the degree of liver fibrosis was assessed by sirius red staining, and the degree of inflammation and fibrosis in the liver was also quantified by immunohistochemical staining. Result B-ob / ob mice had some fat accumulation and ballooning in the liver under normal dietary conditions without any induction. After 6 weeks of HFMCD induction, liver ALT was significantly elevated and liver fibrosis was increased. 12 weeks after WD induction, HE staining analysis showed some degree of intralobular inflammation in the liver in addition to steatosis and ballooning. After WD combined with carbon tetrachloride induction, HE staining showed that liver steatosis, ballooning and intralobular inflammatory features were more obvious, and liver fibrosis was also significantly increased, immunohistochemical result showed a significant increase in F4 / 80, a marker of hepatic macrophages, and α-SMA, a marker of hepatic stellate cell activation. Conclusion B-ob / ob induced by the combination of WD and CCL4 can mimic the pathological features of NAFLD more comprehensively in a short period of time, and is a better animal model of NASH.

Key words: ob / ob mice, non-alcoholic fatty liver disease, animal model