Comparison of two methods for establishing non-alcoholic fatty liver disease model in mice / 中国药理学通报

ABSTRACT

Aim To compare the effects of two different methods of establishing non-alcoholic fatty liver disease ( NAFLD) model, and to explore a more efficient method for establishing NAFLD model that conforms to the characteristics of human disease.Methods C57BL/6J mice were randomly divided into NI) group, WD group, WD combined with CC14 group.'Hie NI) group was fed a normal maintenance diet, and WD group was fed WD.On the basis of WD feed, mice in WD + CC14 group were intraperitoneally injected with CC14 oil solution.'Hie mice were sacrificed on 6, 11 and 16 weeks after modeling.HE staining and oil red 0 staining were performed to observe the pathological changes of liver.The serum levels of ALT, AST, TG and T- CHO were detected by automatic biochemical analyzer, and the levels of IL-lp, IL-6 and TNF-a in liver homogenate were detected by ELISA.The protein expression of FAS and a-SMA was detected by Western blot.Results As the development of model, pathological results showed that NAFLD model was success-fully established by these two methods.At the same time point of modeling, compared with WD group, the liver pathology of WD + CC14 group was more serious, liver steatosis appeared since 6th week.The serum ALT, AST levels and the contents of TG and T-CHO significantly increased.Meanwhile, the levels of inflammatory cytokines obviously increased in the liver, the expression of fibrosis-associated protein a-SMA increased, and the model could progress to the stage of NASH on 16th week.The course of NAFLD in the WD group progressed slowly, and steatosis appeared on 1 1 th week, and it was further aggravated till 16th week.The pro-tein level of FAS was significantly higher than that in WD + CC14 group, and no obvious inflammatory cell infiltration was observed.Conclusions WD feed combined with CC14 to establish NAFLD model takes shorter time and exerts better effect than feeding WD a- lone.It can progress to NASH on 16th week, which can be used as an ideal method to establish NAFLD model.