Effect of oxymatrine on murine fulminant hepatitis and hepatocyte apoptosis

摘要

Objective To evaluate the protective effects and mechanism of action of oxymatrine (OM) on the experimental fulminant hepatitis (FH) and early hepatocyte apoptosis in murine liver tissue. Methods Fulminant hepatitis mice were induced by injecting lipopolysaccharide (LPS) intraperitoneally (ip) in galactosamine (GaIN) sensitized mice. Two separate experiments were designed, including saline control group, fulminant hepatitis group and oxymatrine pretreated group (50 mg/kg, intraperitoneally, bid x 3 days). The levels of serum tumor necrosis factor alpha (TNFa) in mice from two experiments were determined at 5-hour and 7.5-hour after injecting galactosamine/lipopolysaccharide. Mouse liver samples at 5-hour time point were obtained for in situ end labeling (ISEL) staining and ultrastructural observation of apoptotic cells under transmission electron microscope (TEM). Liver samples at 7.5-hour time point were taken for hematoxylin-eosin (HE) staining and immunohistochemical staining of Fas and its ligand (FasL). Results As compared with the fulminant hepatitis group, the levels of serum tumor necrosis factor alpha in mice from the OM pretreated group at 5-hour and 7.5-hour time point were all significantly decreased (P< 0.05 and P < 0.01 respectively) . Hepatocyte apoptosis in mice at 5-hour time point was significantly inhibited (P < 0.01). Both the degree of liver injury and the degree of Fas and Fas ligand expression in the OM pretreated group were reduced remarkably (P < 0.01 and 0.05 respectively) when compared with the saline control group. Conclusions Oxymatrine protects mice from fulminant hepatitis induced by GalN/LPS and may block hepatocyte apoptosis and subsequent necrosis through downregulating the production of serum tumor necrosis factor alpha and the expression of Fas and Fas ligand in liver tissue.