Abstract
Aims To establish a mouse model of non-alcoholic steatohepatitis (NASH) within liver fibrosis using a high-fat and high-carbohydrate diet (HFHC) and to analyze potential pathogenesis using a transcriptome microarray. Methods Sixty mice were stratified by weight and randomly divided into HFHC model and control (Con) groups, with 30 mice in each group. Both HFHC and Con mice were euthanized at 0, 20 and 30 weeks. The following analyses were performed: biochemical analysis; histological assessment; Col-I, α-SMA and TGF-β1 protein and mRNA expression levels; and transcriptomic gene chip analysis. Results Compared with the Con group at each time point, the body weight and liver wet weight of the HFHC model group mice were significantly higher. At 30 weeks, ALT, AST, FBG and FINS levels or activities and TG and HYP contents in the HFHC model group were significantly elevated. Severe steatosis was present in the liver tissues from HFHC group mice. Substantial perisinusoidal fibrosis with a cage-like structure and bridging formations were observed in the liver. Col-I, α-SMA and TGF-β1 protein and mRNA expression levels in liver tissues from HFHC mice increased over time. Compared with the Con group, the HFHC group had 151 differentially expressed genes that were involved in 41 signaling pathways. Conclusions After 30 weeks of a HFHC diet, the mice exhibited substantial liver fibrosis, hepatic steatosis, ballooning degeneration and inflammation. The formation of an experimental NASH combined with liver fibrosis mouse model may be related to ECM-receptor interaction, Toll-like receptor signaling and other signaling pathways.
Placental extract ameliorates liver fibrosis in a methionine- and choline-deficient diet-induced mouse model of non-alcoholic steatohepatitis
