摘要
AIM To study the effect of hepatocyteapoptosis and necrosis induced by TNF-α on thepathogenesis of acute severe hepatitis(ASH).METHODS The model of ASH was prepared inD-galactosamine(GAIN)sensitized BALB/c miceby injection of either endotoxin(ET)or tumornecrosis factor-α(TNF-α).Morphologicalchanges of apoptotic hepatocytes were studiedby both light and electron microscope and in siteend labeling method(ISEL).Molecular biologicalchanges of DNA ladder were observed byelectrophoresis of extract from liver tissues.Biochemical changes were measured by alanineaminotransferase(ALT),asparticaminotransferase(AST)and TNF-α.The relationbetween apoptosis and necrosis was evaluatedsimultaneously.RESULTS The sequence of hepatocyteapoptosis,necrosis,and final death from ASHwas observed both in GAIN/ET and GAIN/TNF-agroup.Apoptosis was prominent at 3.5 h and 5 hafter injection of inducer,while necrosis becamedominant at 9 h after challenge.The appearanceof apoptosis was earlier in GAIN/TNF-α groupthan that in GAIN/ ET group.Pretreatment ofmice with antiTNF IgG1 may completely preventthe liver injury induced by GalN/ET.CONCLUSION TNF-α can cause liver damageby inducing hepatic apoptosis and necrosis inmice with endotoxemia.
AIM To study the effect of hepatocyte apoptosis and necrosis induced by TNF-α on the pathogenesis of acute severe hepatitis(ASH). METHODS The model of ASH was prepared in D-galactosamine(GAIN)sensitized BALB/c mice by injection of either endotoxin(ET)or tumor necrosis factor-α(TNF-α).Morphological changes of apoptotic hepatocytes were studied by both light and electron microscope and in site end labeling method(ISEL).Molecular biological changes of DNA ladder were observed by electrophoresis of extract from liver tissues. Biochemical changes were measured by alanine aminotransferase(ALT),aspartic aminotransferase(AST)and TNF-α.The relation between apoptosis and necrosis was evaluated simultaneously. RESULTS The sequence of hepatocyte apoptosis,necrosis,and final death from ASH was observed both in GAIN/ET and GAIN/TNF-a group.Apoptosis was prominent at 3.5 h and 5 h after injection of inducer,while necrosis became dominant at 9 h after challenge.The appearance of apoptosis was earlier in GAIN/TNF-α group than that in GAIN/ ET group.Pretreatment of mice with antiTNF IgG1 may completely prevent the liver injury induced by GalN/ET. CONCLUSION TNF-α can cause liver damage by inducing hepatic apoptosis and necrosis in mice with endotoxemia.
