摘要
Objective Berberine(BBR)has emerged as a promising therapeutic agent for nonalcoholic fatty liver disease(NAFLD).This study aims to elucidate the underlying molecular mechanisms.Methods In this study,db/db mice were chosen as an animal model for NAFLD.A total of 10 healthy C57BL/6J mice and 30 db/db mice were randomly allocated to one of 4 groups:the normal control(NC)group,the diabetic control(DC)group,the Metformin(MET)therapy group,and the BBR therapy group.The total cholesterol(TC),triacylglycerol(TG),low-density lipoprotein cholesterol(LDL-c),high-density lipoprotein cholesterol(HDL-c),aspartate aminotransferase(AST)and alanine aminotransferase(ALT)levels in the serum were measured.The glutathione peroxidase(GSH-Px),glutathione(GSH),malondialdehyde(MDA),superoxide dismutase(SOD),catalase(CAT),interleukin(IL)-1β,tumor necrosis factor(TNF)-αand monocyte chemotactic protein 1(MCP-1)levels in liver tissue were measured.Hematoxylin and eosin(H&E),acid-Schiff(PAS)and TUNEL stanning was performed for histopathological analysis.Western blotting and immunohistochemistry were conducted to detect the expression levels of key proteins in the AMPK/SIRT1 pathway.Results BBR could improve lipid metabolism,attenuate hepatic steatosis and alleviate liver injury significantly.The excessive oxidative stress,high levels of inflammation and abnormal apoptosis in db/db mice were reversed after BBR intervention.BBR clearly changed the expression of AMP-activated protein kinase(AMPK)/Sirtuin 1(SIRT1),and their downstream proteins.Conclusion BBR could reverse NAFLD-related liver injury,likely by activating the AMPK/SIRT1 signaling pathway to inhibit oxidative stress,inflammation and apoptosis in hepatic tissue.
基金
supported by grants from the National Natural Science Foundation of China(No.81803799)
Hubei Province Natural Science Foundation of China(No.2022CFB092).
