Effect of oxymatrine on murine fulminant hepatitis and hepatocyte apoptosis |
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Authors: | Xiang Xiaoxing Wang Guojun Cai Xiong Li Yuli |
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Affiliation: | Department of Infectious Diseases,Changzheng Hospital,Second Military Medical University, Shanghai 200003, China;Department of Infectious Diseases,Changzheng Hospital,Second Military Medical University, Shanghai 200003, China;Department of Infectious Diseases,Changzheng Hospital,Second Military Medical University, Shanghai 200003, China;Department of Pathology, Changzheng Hospital,Second Military Medical University, Shangh ai 200003, China |
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Abstract: | Objective To evaluate the protective effects and mechanism of action of oxymatrine (OM) on the experimental fulminant hepatitis (FH) and early hepatocyte apoptosis in mur ine liver tissue.Methods Fulminant hepatitis mice were induced by injecting lipopolysaccharide (LPS) intr aperitoneally (ip) in galactosamine (GalN) sensitized mice.Two separate experim ents were designed, including saline control group, fulminant hepatitis group an d oxymatrine pretreated group (50mg/kg, intraperitoneally, bid×3 days) . The leve ls of serum tumor necrosis factor alpha (TNFa) in mice from two experiments were determined at 5-hour and 7.5-hour after injecting galactosamine/lipopolysacc haride. Mouse liver samples at 5-hour time point were obtained for in situ end labeling (ISEL) staining and ultrastructural observation of apoptotic cells und er transmission electron microscope (TEM). Liver samples at 7.5-hour time poi nt were taken for hematoxylin-eosin (HE) staining and immunohistochemical stain ing of Fas and its ligand (FasL). Results As compared with the fulminant hepatitis group, the levels of serum tumor necros is factor alpha in mice from the OM pretreated group at 5-hour and 7.5-hour t ime point were all significantly decreased (P<0.05 and P<0.01 respecti vely). Hepatocyte apoptosis in mice at 5-hour time point was significantly inh ibited (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 bl ock hepatocyte apoptosis and subsequent necrosis through downregulating the prod uction of serum tumor necrosis factor alpha and the expression of Fas and Fas li gand in liver tissue. |
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Keywords: | oxymatrine fulminant hepatitis apoptosi s Fas antigen Fas ligand |
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