JAK/STAT通路在脂多糖诱导肝细胞HMGB1释放中的作用  

Effect of JAK/STAT signaling pathway on extracellular release of HMGB1 in lipopolysaccharide-induced hepatocytes

作　　者：张健[1] 帅朝霞[1] 胡志刚[1] 王春新[1] 袁劲松[1] 陈国千[1] 

机构地区：[1]南京医科大学附属无锡人民医院检验科,江苏无锡214023

出　　处：《南京医科大学学报（自然科学版）》2009年第11期1514-1516,1533,共4页Journal of Nanjing Medical University(Natural Sciences)

基　　金：江苏省自然科学基金(BK2006027);教育部留学回国人员科研启动基金资助项目

摘　　要：目的:探讨Janus激酶/信号转导和转录激活子(JAK/STAT)信号通路在内毒素脂多糖诱导肝细胞高迁移率族蛋白B1(HMGB1)释放中的作用。方法:观察100μg/L脂多糖诱导后,大鼠肝细胞BRL-3A细胞HMGB1 mRNA表达水平和细胞培养上清液中HMGB1含量的变化,及不同浓度的JAK/STAT通路抑制剂tyrphostin AG490、氟达拉滨的影响。结果:脂多糖诱导BRL-3A细胞24h后HMGB1 mRNA表达水平和培养上清液中HMGB1含量明显升高(P<0.01),25μmol/L tyrphostin AG490和50μmol/L氟达拉滨对以上2个指标显示一定程度的抑制作用(P<0.05)。结论:内毒素脂多糖可诱导肝细胞HMGB1的表达和释放,其机制可能与细胞JAK/STAT信号通路有关。Objective：To study the effect of JAK/STAT signaling pathway on extracellular release of high mobility group box 1 （HMGB1） in endotoxin-induced hepatocytes, nethods：HMGB1 concentration was determined in the culture medium of 100 μg/L lipopolysaccharide-induced BRL-3A hepatocytes by enzyme-linked immunosorbent assay （ELISA）, and the change of HMGB1 mRNA expression was detected by RT-PCR method. The effects of JAK/STAT pathway inhibitors （tyrphostin AG 490 and fludarabine） with various concentrations on HMGB 1 mRNA expression and extracellular release were investigated. Results：The level of HMGB1 mRNA expression and HMGB1 concentration in the culture medium significantly increased after BRL-3A hepatocytes induced by lipopolysaccharide for 24 hours （P 〈 0.01）. 25 μmol/L tyrphostin AG 490 and 50 μmol/L fludarabine partly inhibited HMGB1 mRNA expression and extracellular release in lipopolysaccharide-induced BRL-3A hepatocytes （P 〈 0.05）. Conclusion：Lipopolysaccharide induces hepatocytes to release HMGB1 ,which is related to intracellular JAK/STAT signaling pathway.

关 键 词：高迁移率族蛋白B1 肝细胞 内毒素 JANUS激酶 信号转导和转录激活子 

分 类 号：R392.1[医药卫生—免疫学]