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Effect of hepatocyte apoptosis induced by TNF-α on acute severe hepatitis in mouse models

查看全文 作  者:Guo Qing Zang Xia Qiu Zhou Hong Yu Qing Xie Guo Ming Zhao Bin Wang Qing Guo Yue Qin Xiang Dan Liao Department of Infectious Diseases,Rujin Hospital,Shanghai Second Medical University,Shanghai 200025,China 高影响力作者 出  处:《World Journal of Gastroenterology》索引2000年第6卷第5期,共5页高影响力期刊 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. 关 键 词:tumor NECROSIS factor HEPATITIS apoptosis ALANINE TRANSAMINASE ASPARTATE TRANSAMINASE ENDOTOXINS mice
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