萝卜硫苷对乙型病毒性肝炎小鼠模型的影响及机制研究OA

Objective:This study aims to investigate the effect of glucoraphanin on hepatitis B virus(HBV)repli-cation and immunoregulation in HBV-carrying mice and preliminarily explore its mechanism of action.Methods:A mouse model of HBV transfection was established using high-pressure hydrodynamic injection.Mice were randomly di-vided into a normal control group,a model control group,and glucoraphanin treatment groups at doses of 10 mg/kg,25 mg/kg,and 50 mg/kg.Serum levels of hepatitis B surface antigen(HBsAg),hepatitis B e antigen(HBeAg),inter-feron-γ(IFN-γ),alanine aminotransferase(ALT),aspartate aminotransferase(AST),and HBV DNA load were detec-ted by enzyme-linked immunosorbent assay(ELISA).Hepatitis B core antigen(HBcAg)protein expression in liver tis-sue was detected by immunohistochemistry.The proportion of CD4+IFN-γ+T cells in splenic lymphocytes was analyzed by flow cytometry.Western blotting was used to detect the expression of Toll-like receptor 2(TLR2),nuclear factor-κB p65(NF-κB p65),NOD-like receptor protein 3(NLRP3),apoptosis-associated speck-like protein(ASC),cleaved caspase-1(C-caspase-1),and interleukin-1β(IL-1β)in liver tissues.Hematoxylin-eosin(HE)staining was used to de-tect histopathological changes of liver tissue.Results:Compared with the normal control group,mice in the model control group showed significantly increased serum levels of HBsAg,HBeAg,HBV DNA load,and HBcAg protein expression in liver tissues(P<0.05).Meanwhile,serum IFN-γ levels and the proportion of CD4+IFN-γ+T cells in splenic lympho-cytes were decreased(P<0.05),and the expression levels of TLR2,NF-κB p65,NLRP3,ASC,C-caspase-1,and IL-1β proteins in liver tissues were significantly downregulated(P<0.05).Compared with the model control group,mice in the 25 mg/kg and 50 mg/kg glucoraphanin groups showed significantly decreased serum levels of HBsAg and HBeAg,lower HBV DNA load,and reduced expression of HBcAg protein in liver tissues(P<0.05).Additionally,serum IFN-γ levels and the proportion of CD4+IFN-γ+T cells in splenic lymphocytes were increased(P<0.05),and the expression levels of TLR2,NF-κB p65,NLRP3,ASC,C-caspase-1,and IL-1β proteins in liver tissues were significantly upregulated(P<0.05).Histopathological examination revealed normal liver cell structure and no obvious pathological damage in all groups.Conclusion:Glucoraphanin can exert anti-HBV effects,which may be related to the activation of the TLR2/NF-κB/NLRP3 signaling pathway and the enhancement of innate immune function.