Intervention Effect and Mechanism of Celastrol on NASH Induced by Methionine-choline Deficiency Diet in Mice / 中国药房

ABSTRACT

OBJECTIVE：To study the intervention eff ects and pot ential m echanism of celastrol on non-alcoholic steatohepatitis （NASH）induced by methionine-choline deficiency （MCD）diet. METHODS ：Male C 57BL/6J mice were randomly divided into normal control group ，model group ，celastrol low-dose and high-dose groups [ 0.5，1 mg/（kg·d）]，with 7 mice in each group. The normal control group was given a methionine-choline sufficient diet ，while the model group and administration groups were fed an MCD diet to induce NASH model. At the same time ，normal control group and model group were given polyoxyethylene castor oil intragastrically；administration groups were given relevant drugs intragastrically ；the volume of gavage was 0.1 mL/g，once a day ， for consecutive 4 weeks. The liver morphology was observed ，and the pathological changes of liver tissue were observed by HE staining and oil red O staining. The levels of serum liver enzymes （AST，ALT），and the levels of lipid indexes （TC，TG）in serum and liver tissue were detected by enzyme method. The protein expression of NF-κB p65，TNF-α and IL-6 in liver tissue were determined by Western blotting assay. RESULTS ：Compared with normal control group ，the volume of the liver was reduced and the color was yellow ，and the surface was rough in model group ；inflammatory cell infiltration ，fat vacuoles and lipid droplets aggregation were found in the liver tissue ；the serum levels of TC and TG were significantly decreased ，the levels of serum liver enzymes and protein expression of NF-κB p65，TNF-α and IL-6 in liver tissue were significantly increased （P＜0.01）. Compared with model group ，the liver surface of each administration group was ruddy and smooth without brown spots ，the inflammatory cells and fat vacuoles in liver tissue were reduced ，and the coverage area of lipid droplets was reduced ；the levels of serum TC and TG were significantly increased ，the levels of serum liver enzymes ，the levels of TG and protein expression of NF-κB，TNF-α and IL-6（except for celastrol low-dose group ）in liver tissue were significantly decreased （P＜0.05 or P＜0.01）. CONCLUSIONS ： Celastrol can improve the liver injury of NASH model mice induced by MCD diet ，which is related to the reduction of TG accumulation in liver tissue and inhibition of the expression of inflammatory related factors.