ABSTRACT
AIM To explore the protective effects and mechanisms of dihydromyricetin (DHM) against non-alcoholic fatty liver disease (NAFLD) in ApoE-/-mice.METHODS The 40 male healthy six week-old ApoE-/mice were randomly divided into model group,DHM (50,100 mg/kg) group and Bicyclol group.Ten male C57 mice were used as the control group.The control and model groups were administrated with 0.5％ CMC-Na solution and the other three groups were given DHM [50,100 mg/(kg-d),i.g.] and Bicyclol [140 mg/(kg · d),i.g.].All mice were fed with high fat diet (0.3％ cholesterol,20％ fat) for 12 weeks.At the end of the experiment,the blood was collected from the orbit and the serum was separated for blood lipid detection.AST and ALT expression levels were detected by automatic biochemical analyzer.HE staining and oil red O monitored the liver injury and lipid accumulation.The oxidase enzymes were measured by the commercial kits.The hepatocyte apoptosis was determined by TUNEL assay,and the Bcl-2,Caspase-3 expression levels were detected by immunohistochemistry.The AMPK and phosphorylation of AMPK expression levels were determined by Western blot.RESULTS After the treatment,liver lipid accumulation and liver injury,TUNEL postive cells sharply increased compared with the control group.Meanwhile,the Caspase-3 expression level was significantly upregulated and the Bcl-2 was markedly downregulated in the model group.DHM [50,100 mg/(kg · d)] remarkably reduced AST and ALT levels,liver lipid accumulation and TUNEL positive cells and modulated oxidase enzymes expression level compared with the model group.Moreover,DHM obviously increased Bcl-2 expression and decreased Caspase-3 expression in liver tissue,and inhibited AMPK phosphorylation.CONCLUSION DHM reduces the lipid accumulation and protects liver injury from high fat diet induced NAFLD mice,the protective mechanism of DHM may be related to inhibiting AMPK phosphorylation and inhibiting hepatocyte apoptosis.