HMGB1在内毒素血症小鼠肝损伤中的作用

Effect of high mobility group box 1 on liver damage in mice with endotoxemia

目的探讨高迁移率族蛋白B1(HMGB1)在内毒素血症小鼠肝损伤中的作用。方法BALB/c小鼠随机分为正常对照组0、.2 mg/kg脂多糖组、1 mg/kg脂多糖组5、mg/kg脂多糖组、AG 490处理组和氟达拉宾处理组,AG 490和氟达拉宾的使用剂量分别为20 mg/kg和10 mg/kg。于腹腔注射后不同时间观察肝组织HMGB1 mRNA表达、血清HMGB1水平和丙氨酸氨基转移酶、天门冬氨酸氨基转移酶活力的变化。HMGB1 mRNA表达和HMGB1含量分别采用RT-PCR方法和ELISA检测。结果小鼠注射脂多糖后,肝组织HMGB1 mRNA表达、血清HMGB1水平和丙氨酸氨基转移酶、天门冬氨酸氨基转移酶活力均呈剂量相关性升高,而使用JAK/STAT通路抑制剂AG 490和氟达拉宾处理后,以上指标均明显下降(P<0.05)。结论脂多糖诱导的HMGB1释放与胞内JAK/STAT信号通路有关,HMGB1在内毒素血症小鼠肝损伤中具有作用。

Objective To study the effect of high mobility group box 1（HMGB1） on liver damage in mice with endotoxemia.Methods The BALB/c mice were randomly divided into normal control group,0.2 mg/kg lipopolysaccharide（LPS） group,1 mg/kg LPS group,5 mg/kg LPS group,1 mg/kg LPS group treated with 20 mg/kg tyrphostin AG 490 and 1 mg/kg LPS group treated with 10 mg/kg fludarabine.The changes were investigated at different hours after intraperitoneal injection for HMGB1 mRNA expression in liver tissue,serum HMGB1 level,and serum activities of alanine aminotransferase and aspartate aminotransferase.HMGB1 mRNA expression and HMGB1 concentration were determined by RT-PCR and enzyme-linked immunosorbent assay（ELISA）,respectively.Results The Results significantly increased LPS dose-dependently for HMGB1 mRNA expression in liver tissue,serum HMGB1 level,and serum activities of alanine aminotransferase and aspartate aminotransferase,after the mice were intraperitoneally injected with LPS,which was attenuated by JAK/STAT pathway inhibitors（tyrphostin AG 490 and fludarabine）（P〈0.05）.Conclusion Intracellular JAK/STAT signaling pathway is involved in LPS-induced HMGB1 release.HMGB1 may play a role in LPS-induced liver damage in mice.