Metabolic dysfunction-related steatohepatitis (MASH) is typically characterized by obesity, insulin resistance, steatohepatitis, hepatocellular ballooning, fibrosis, and atherosclerosis. The MASH models often used in preclinical experiments include genetic animal models, diet-induced animal models, and animal models constructed by combination of genetic and diet-induced animal models. In order to understand the pathogenesis of MASH and develop innovative therapies, Vitalstar has developed several mouse models of MASH at different stages of its pathogenesis.

(1) MASH mouse model induced by HFMCD and its drug efficacy evaluation

1. Experimental scheme

C56BL/6 mice were fed a high-fat methionine choline deficiency diet (HFMCD, dietary composition containing 60 kcal% fat, methionine and choline deficiency) for 4-6 weeks.

2. Experimental data

Serum ALT and AST concentrations; HE staining and NAS score of liver tissue sections; Liver tissue sections were stained with Sirius scarlet and liver fibrosis degree statistics.

(2) STAM-MASH model and its drug efficacy evaluation

1. Experimental scheme

C57BL/6J male mice were given a single subcutaneous injection of 200ug STZ (Sigma), and were continuously induced from 4 weeks of age to 20 weeks of age, and fed the HFD32 diet to induce MASH-HCC.

2. Experimental data

Changes of body weight and blood glucose after induction; HE staining of liver tissue; Frozen slice oil red staining; The blood biochemical results showed the characteristics of STAM model (ALT, AST, TG, TC). NAFLD activity score; Sirius scarlet staining and IHC staining; Quantitative data for colus scarlet and IHC staining (α-SMA, F4/80).

(3) The MASH model of C57BL/6 aged mice induced by GAN diet and its drug efficacy evaluation

1. Experimental scheme

Aging C57BL/6 mice (56 weeks of age) were fed GAN diet for 12-24 weeks, and the actual feeding time was determined according to the experimental purpose.

2. Experimental data

Body weight, glucose tolerance test (AUC), plasma insulin content, HE staining, frozen section oil red staining, NAS score, Sirius scarlet staining, and flow analysis of different liver immune cells were observed regularly.

(4) The MASH model of C57BL/6 mice induced by GAN diet and its drug efficacy evaluation

1. Experimental scheme

C57BL/6 mice (6 weeks of age) fed GAN diet for 12-34 weeks showed steatosis at 10-12 weeks, hepatocellular balloon-like degeneration and lobular inflammation at 16-20 weeks, and fibrosis at 24-34 weeks. The actual induction time depends on the experimental needs.

2. Experimental data

Body weight, glucose tolerance test (AUC), plasma insulin content, HE staining, frozen section oil red staining, NAS score and Sirius scarlet staining were observed regularly.

(5)The MASH model of HBV-Tg mice induced by GAN diet and its drug efficacy evaluation

1. Experimental scheme

HBV-Tg mice (6-8 weeks of age) fed GAN diet for 8-30 weeks, HBV-Tg mice were more sensitive than wild C57BL/6 mice fed D09100310 diet, and showed hepatic steatosis (8-20 weeks) and hepatic fibrosis (20-34 weeks). If HBV-Tg mice and CCL4 are used to induce hepatitis B liver fibrosis, the mouse model can be successfully established in 8-10 weeks. The actual induction time depends on the experimental needs.

2. Experimental data

Body weight, glucose tolerance test (AUC), plasma insulin content, HE staining, frozen section oil red staining, NAS score and Sirius scarlet staining were observed regularly.

(6) B6-Alms1 MASH model and its drug efficacy evaluation

1. Experimental scheme

The B6-Alms1 mice were fed a Western diet, and the mutant mice developed typical symptoms of MASH within a short period of time (4~6 weeks) when fed a Western diet.

2. Experimental data

Body weight, liver anatomy, plasma cholesterol and low density lipoprotein cholesterol levels, liver triglyceride and total cholesterol levels, plasma liver enzymes, liver histology (HE staining, oil red O staining, scarlet scarlet staining) were measured at regular intervals.

(7) The MASH model induced by HFD+CCL4 and its drug efficacy evaluation

1. Experimental scheme

C57BL/6 mice were fed HFD/WD diet for 10-12 weeks, followed by CCL4 injection for 4-6 weeks (ip, BIW)..

2. Experimental data

Body weight, liver anatomy, blood biochemical indexes (ALT, AST, TG, TC, LDL-C, HDL-C), and pathological tissue detection (HE staining, oil red O staining, and scarlet scarlet staining) were regularly observed.