氧化苦参碱对小鼠暴发型肝炎及肝细胞凋亡作用的研究
Effect of oxymatrine on murine fulminant hepatitis and hepatocyte apoptosis
目的观察氧化苦参碱(oxymatrine,OM)对实验性小鼠暴发型肝炎(fulminant hepatitis,FH)及其早期肝细胞凋亡的保护作用,并研究其药理机制.方法腹腔注射(ip)脂多糖(LPS)+氨基半乳糖(GalN)造成小鼠FH模型.两次实验均设生理盐水对照组、暴发型肝炎组和OM预保护组(50 mg/kg,ip,bid×3d).分别于注射GalN/LPS后5 h、7.5 h取血清检测肿瘤坏死因子(TNFα),同时在5 h点取肝组织作原位凋亡细胞检测,并于电镜下观察凋亡细胞超微结构;在7.5 h点取肝组织作HE染色及Fas及其配体(FasL)的免疫组化检测.结果与模型组相比,OM治疗组5 h、7.5 h点TNFα水平明显减低(P<0.05和0.01),5 h点肝细胞凋亡亦明显减少(P<0.01).OM组7.5 h点肝组织损伤及Fas、FasL表达程度均较模型组减轻(P<0.01和P<0.05).结论 OM对GalN/LPS诱导的小鼠FH有保护作用,其机制可能为抑制TNFα释放及Fas、FasL表达,从而阻断肝细胞凋亡及坏死.
更多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 (GalN) sensitized mice.Two separate experiments were designed, including saline control group, fulminant hepatitis group and oxymatrine pretreated group (50mg/kg, intraperitoneally, bid×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.
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