肝损伤模型小鼠高迁移率族蛋白-1的表达  

The Expression of HMGB1 on Con A Mouse Models of Experimental Heptitis

作　　者：刘洪波[1] 范学工[1] 刘悦晖[1] 张磐[1] 周蓉蓉[1] 李宁[1] WANG Hai-chao 黄建军 

机构地区：[1]中南大学湘雅医院传染科,中国湖南长沙410008 [2]Department of Emergency Medicine, North Shore University Hospital, New York 11030, USA [3]中国湖南长沙410008,中国湖南长沙410008

出　　处：《生命科学研究》2008年第2期168-173,共6页Life Science Research

基　　金：国家-高校博士点基金新教师项目(20070533009);湖南省自然科学基金资助项目(06JJ50166)

摘　　要：将刀豆蛋白A(Con A)经尾静脉注射入雄性Balb/C小鼠,建立T细胞介导的Con A急性肝损伤小鼠模型,检测模型小鼠不同时间点血清中高迁移率族蛋白1(HMGB1)及肝组织HMGB1mRNA的表达水平,并与血清中TNF-α进行对比.实验显示:在Con A注射后0～3h,小鼠血清中的未能检测出HMGB1蛋白特异带;但在4h后,检测出一条微弱的HMGB1蛋白特异带;在6～36h,均检测出一条清晰的HMGB1蛋白特异带,在8￣12h处于一个高水平状态.而正常对照组小鼠血清中未能检测HMGB1蛋白.与HMGB1动力学曲线不同,血清中TNF-α水平在Con A注射后2h就达到峰值,4h后迅速下降,8h恢复到正常范围.Con A小鼠肝细胞中HMGB1mRNA的表达在Con A注射1h后即达到峰值,是对照组的2.4倍,之后迅速回落,3～12h均低于对照组水平(0.5～0.8倍),24h后逐渐恢复正常水平.初步揭示HMGB1在Con A小鼠急性肝损伤中可能发挥重要作用,血清中HMGB1蛋白与TNF-α相比,呈现出迟发与长效的特点,HMGB1给肝细胞造成损伤有足够强度和效应时间.To investigate whether there is a possible role of the late pro-inflammatory cytokine high mobility group box protein 1 （HMGB1） on acute liver injury mediated by T Cell of coneanavalin A （ Con A ） mouse models of experimental heptitis. The kineticses of serum HMGB1 and TNF-α on Con A mouse models of experimental heptitis with different time point after Con A challenge were described, and liver HMGB1 mRNA levels of the experiment animals were also determined. The results showed as follows： 1 ） No serum HMGB1 was detected at 0, 2 and 3 h after Con A challenge, while a slender band of HMGB1 was found at 4 h and serum HMGB1 was maintained at peak, plateau levels from 8 to 24 hours after Con A challenge. Determination of plasma TNF concentrations revealed that a peak TNF expression was detectable within the second hour after Con A challenge and TNF expression in plasma was deceased rapidly at 4 h after challenge and was recovered near normal level at 8 h; 2） A 2.4 folds peak HMGB1 mRNA expression was detected within 1 h after Con A treatment when compared with NaCl-injected controls. HMGB1 mRNA levels began to resilience at 2 h and returned to normal levels at 12 h after challenge. It could be conclued that： HMGB1 was a key mediator on the experimental Con A-induced acute liver injury model and it showed late onset and long acting characteristics compared with serum TNF-α. The injure to hepatocyte with sufficient effect time and strength could be provided by serum HMGB 1.

关 键 词：刀豆蛋白A 肝损伤模型 晚期炎症介质 高迁移率族蛋白-1 

分 类 号：R3[医药卫生—基础医学]