刀豆蛋白A诱导的急性肝损伤小鼠血浆细胞外组蛋白的变化及意义  

Plasma extracellular histones changes in concanavalin A-induced acute liver injury in mice

作　　者：温韬[1] 刘焱[1] 任锋[1] 朴正福[1] 陈德喜[1] 

机构地区：[1]首都医科大学附属北京佑安医院/北京市肝病研究所,北京市100069

出　　处：《实用肝脏病杂志》2015年第3期278-281,共4页Journal of Practical Hepatology

基　　金：国家自然科学基金项目(编号:81372094);北京市卫生系统高技术人才培养项目/学科骨干培养项目(编号:2013-3-077)

摘　　要：目的研究细胞外组蛋白在刀豆蛋白A(Con A)诱导的小鼠急性肝损伤时的水平变化及干预价值。方法小鼠经尾静脉注射Con A(35 mg·kg-1)建立急性肝损伤模型,同时给予特异性抗组蛋白中和抗体进行干预,比较两组小鼠的存活率、肝功能以及相关细胞因子水平的变化。结果给予小鼠Con A后,染毒3 h、9 h、16 h和24h时血清ALT水平升高为(106.5±25.5)IU/L、(769.1±138.2)IU/L、(1340.2±205.9)IU/L和(1304.7±300.7)IU/L,均明显高于对照组[(35.5±3.165)IU/L,P<0.01];肝组织病理学检查显示有大量肝细胞发生变性、坏死;Con A染毒小鼠血浆细胞外组蛋白水平亦呈时间依赖方式明显增高,染毒3 h、9 h、16 h和24 h时,细胞外组蛋白相对水平分别为(1.199±0.1087)、(2.467±0.197)、(2.655±0.2295)和(2.631±0.3014),显著高于对照组水平[(0.206±0.024),P<0.001];染毒小鼠经特异性抗组蛋白中和抗体干预后,死亡率明显下降,病理学显示肝损伤程度亦得到减轻,其血清IL-6和TNF-α水平分别为(16.98±3.67)pg/ml和(3.25±0.67)pg/ml,较模型组水平显著降低[分别为(238.10±48.56)pg/ml和(16.52±2.43)pg/ml,P<0.01]。结论细胞外组蛋白是Con A所致急性肝损伤发病过程中的重要炎性介质,以细胞外组蛋白为靶点进行干预能减轻肝脏炎症反应。Objective To investigate extracellular histones changes in concanavalin A（Con A）-induced acute liver injury in mice as well as the intervening potential on targeted histones. Methods Acute liver injury was induced by Con A injection via tail vein at a dose of 35 mg·kg-1body 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 Con A 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,P0.01 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 Con A,and intervention targeting extracellular histones shows promising potential in the relief of hepatic inflammatory reaction.

关 键 词：肝损伤 刀豆蛋白A 细胞外组蛋白 细胞因子 小鼠 

分 类 号：R285.5[医药卫生—中药学]