论文部分内容阅读
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。
Objective To observe the protective effect of oxymatrine (OM) on fulminanthepatitis (FH) and its early hepatocyte apoptosis in experimental mice and its pharmacological mechanism. Methods FH mice were induced by intraperitoneal injection of lipopolysaccharide (LPS) + galactosamine (GalN). Two experiments were set saline control group, fulminant hepatitis group and OM pre-protection group (50mg / kg, ip, bid × 3d). Tumor necrosis factor (TNFα) was detected at 5h and 75h after injection of GalN / LPS respectively. At the same time, the hepatocytes were harvested for detection of apoptotic cells at 5h. The ultrastructure of apoptotic cells was observed under electron microscope. The liver tissues were harvested at 5h for HE staining and immunohistochemistry of Fas and its ligand (FasL). Results Compared with the model group, the levels of TNFα in OM group decreased significantly at 5h and 7h (P <0.05 and 0.01), and also decreased at 5h (P <0.01). The liver injury and the expression of Fas and FasL in OM group were lower than those in model group at 5h (P <0.01 and P <0.05). Conclusion OM can protect FH induced by GalN / LPS in mice, and its mechanism may be to inhibit the release of TNFα and the expression of Fas and FasL, thereby blocking the apoptosis and necrosis of hepatocytes.