摘要
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 (50?mg/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
目的 观察氧化苦参碱 (oxymatrine ,OM)对实验性小鼠暴发型肝炎 (fulminanthepatitis,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 (5 0mg/kg ,ip ,bid× 3d)。分别于注射GalN/LPS后 5h、7 5h取血清检测肿瘤坏死因子(TNFα) ,同时在 5h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 5h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 5h、7 5h点TNFα水平明显减低 (P <0 0 5和 0 0 1) ,5h点肝细胞凋亡亦明显减少 (P <0 0 1)。OM组 7 5h点肝组织损伤及Fas、FasL表达程度均较模型组减轻 (P <0 0 1和P <0 0 5 )。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。
