Regulation of proliferation and apoptosis of hepatocytes in mice with acute alcoholic liver injury by ADAM8
Objective To investigate the effects of ADAM8 on hepatocyte proliferation and apoptosis in mice with acute alcoholic liver injury.Methods Thirty KM mice aged 6-8 weeks were randomly divided into 5 groups:normal control group(n=6),model group(n=6),ADAM8-sgRNA1 group(n=6),ADAM8-sgRNA2 group(n=6),and ADAM8-sgRNA3 group(n=6).Mice in normal control group did not receive any treatment,mice in plasmid group were injected with 3 plasmids respectively through tail vein,and mice in model group were injected with the same amount of normal saline through tail vein.Mice in model group and plasmid group were routinely fed for 3 days,and acute liver injury was induced by oral gavage of 14 mL/kg 50%alcohol once.The serum was separated for the determi-nation of AST and ALT.The liver of the mice was stained with HE to observe the histopathological changes and the liver glycogen changes were stained with PAS.The expression levels of ADAM8,TNF-α,PCNA and Bax were detected by Western blotting.Results The expression level of ADAM8 in ADAM8-sRNA2 group was significantly decreased compared with model group(P<0.05).Compared with the normal control group,the expression level of PCNA in the model group was significantly decreased(P<0.001),and the expression levels of TNF-α and Bax were significantly increased(P<0.01).Compared with model group,the expression levels of PCNA in ADAM8-sgRNA2 group were significantly increased(P<0.001),and the expression levels of TNF-α and Bax were significantly decreased(P<0.01 or P<0.001).Compared with normal control group,AST and ALT indexes in model group were significantly increased(P<0.05).Compared with model group,AST and ALT indexes of ADAM8-sgRNA2 group were significantly decreased.The results of HE staining and PAS staining showed that compared with the normal control group,the liver injury was obvious in the model group,the necrosis score was significantly increased(P<0.05),and the glycogen content was significantly decreased(P<0.001).Compared with model group,necrosis score in ADAM8-sgRNA2 group was significantly decreased(P<0.05),and glyco-gen content in ADAM8-sgRNA2 group was significantly increased(P<0.001).Conclusion ADAM8 can inhibit hepato-cyte proliferation and promote hepatocyte apoptosis in mice with acute alcoholic liver injury.
NETL
NSTL
万方数据
