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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 hepatocyteapoptosis 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 miceby injection of either endotoxin Morphological changes of apoptotic hepatocytes were studied by both light and electron microscopy and in siteend labeling method (ISEL). Molecular biological changes of DNA ladders were observed by electrophoresis of extract from liver tissues. Biochemical changes were measured by alanine aminotransferase (ALT), asparticaminotransferase (AST) and TNF-α.The relationbetween apoptosis and necrosis was evaluated as minimally .RESULTS The sequence of hepatocyte apoptosis, 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 grou pthan that in GAIN / ET group. Treatment 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 mouse with endotoxemia.