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目的 研究肿瘤坏死因子 α(tumornecrosisfactor α,TNF α)诱导肝细胞凋亡在暴发性肝衰竭中的作用机制。方法 分别注射脂多糖 (lipopolysaccharide ,LPS)和TNF α于D 氨基半乳糖 (D galac tosamine,GalN)致敏的BALB/c小鼠 ,造成暴发性肝衰竭模型 ,用脱氧核糖核酸转移酶介导的缺口原位末端标记 (insiteendlabeling ,ISEL)技术、电镜及抽提肝组织DNA琼脂糖凝胶电泳检测DNALadder观察肝细胞凋亡 ,同时探索肝细胞凋亡和肝细胞坏死间的关系。结果 GalN/LPS和GalN/TNF α组小鼠均发生肝细胞凋亡、坏死 ,最终因肝功能衰竭死亡。 3.5h～ 6h肝细胞以凋亡为主 ,6h以后则以坏死为主 ,直到小鼠死亡时肝细胞凋亡仍持续存在。预先使用抗TNF α抗体可阻断GalN/LPS介导的肝细胞凋亡、坏死和小鼠死亡。结论 TNF α是内毒素血症中造成肝细胞凋亡的终末介质 ,肝细胞凋亡存在于整个病程中 ,而坏死则在病程后期出现 ,凋亡的肝细胞可能引发了肝细胞坏死
Objective To study the mechanism of hepatocellular apoptosis induced by tumor necrosis factor α (TNFα) in fulminant hepatic failure. Methods BALB / c mice were injected with lipopolysaccharide (LPS) and TNFα in D galactosamine (GalN) -induced model of fulminant hepatic failure, respectively, and were induced by DNA transferase The expression of DNALadder was detected by electron microscopy and electron microscopy, and the DNA was extracted from the extracted liver tissue by electron microscopy. The apoptosis of hepatocytes and the relationship between hepatocyte apoptosis and hepatocyte necrosis were also observed. Results All of the mice in GalN / LPS group and GalN / TNFα group had hepatocellular apoptosis and necrosis, and eventually died of liver failure. 3.5h ~ 6h apoptosis of hepatocytes, mainly after 6h necrosis, until the death of mice hepatocyte apoptosis persists. Pretreatment with anti-TNF α antibody blocked GalN / LPS-mediated hepatocyte apoptosis, necrosis and mouse death. Conclusions TNFα is the terminal mediator of hepatocyte apoptosis in endotoxemia. The apoptosis of hepatocytes occurs throughout the course of the disease, whereas necrosis occurs at the end of the course of disease. Apoptotic hepatocytes may trigger hepatocyte necrosis