关键词: 肝损伤, 刀豆蛋白A, 细胞外组蛋白, 细胞因子, 小鼠

Abstract: Objective To investigate extracellular histones changes in concanavalin A （ConA）-induced acute liver injury in mice as well as the intervening potential on targeted histones. Methods Acute liver injury was induced by ConA injection via tail vein at a dose of 35 mg·kg^-1 body weight in C57BL/6 mice. The animals in intervention group were treated with specific anti-histone neutralizing antibody. The survival rates, hepatic function index and related cytokines in different groups were analyzed. Results In model group, plasma ALT levels at the time point of 3 h,9 h,16 h and 24 h after ConA treatment remarkably increased compared with those in control group [（106.5±25.5） IU/L,（769.1±138.2） IU/L,（1340.2±205.9） IU/L and（1304.7±300.7） IU/L vs. （35.5±3.165） IU/L,P<0.01 for all];the plasma extracellular histones in model group at 3 h,9 h,16 h and 24 h increased considerably in a time-dependent manner as compared with those in control group[（1.199±0.1087）,（2.467±0.197）,（2.655±0.2295）,（2.631±0.3014） vs. （0.206±0.024）,P<0.01 for all];Histology revealed degeneration and necrosis in a great amount of hepatocytes in model group,however,survival rate and liver damage were improved following administration of anti-histone neutralizing antibody;Serum IL-6 and TNF-α levels in intervention group were lower than those in model group[（16.98±3.67） pg/ml vs.（238.10±48.56） pg/ml,（3.25±0.67） pg/ml vs. （16.52±2.43） pg/ml,P<0.05 for both]. Conclusions Extracellular histones are important inflammatory mediators involved in the pathogenesis of acute liver injury induced by ConA,and intervention targeting extracellular histones shows promising potential in the relief of hepatic inflammatory reaction.

Key words: Acute liver injury, Extracellular histones, Concanavalin A, Cytokines, Mice