中文摘要：

目的 阐明高迁移率族蛋白B1（HMGB1）在小鼠急性肝功能衰竭模型肝组织中的表达模式、动态变化及其与TNF-α、IL-1β的相互作用.方法 D-氨基半乳糖和脂多糖制备小鼠急性肝功能衰竭模型,免疫组织化学SABC法检测肝组织内HMGB1在6个时间点的表达变化,ELISA测定血清中TNF-α、IL-1β的含量.配对t检验分析数据差异.结果 造模后2 h肝内即可观察到HMGB1的表达,并随时间的延长而呈现出明显的增长趋势,直至24 h;血清中TNF-α、IL-1β造模后即出现上升,分别于8 h、2 h达到峰值,TNF-α 8 h为（473.42±22.99）pg/mL,IL-1β2 h为（724.49士34.24）pg/mL.后缓慢下降,其中IL-1β于24 h恢复正常为（51.49士36.87）pg/mL.结论 HMGB1是急性肝功能衰竭的重要参与因子,早期可促进TNF-α、IL-1β的分泌,中晚期则在炎性因子的作用下大量表达,加速肝脏损伤,并与肝功能衰竭的发展及严重程度存在正相关.

英文摘要：

Objective To study the expression-mode and dynamic transmutation of high mobility group box-1 （HMGB1） in hepatocytes of the mouse model with acute hepatic failure and to study the interaction beween HMGB1 and tumor necrosis factor-α （TNF-α）, interleukin-1β （IL-1β）. Methods The mouse model of acute hepatic failure was established by injecting D-galactosamine （D-GalN） and lipopolysaccharide（LPS）. Immunohistochemistry SABC method was used to detect the HMGB1 expression at 6 time points. The enzyme linked immunosorbent assay （ELISA） was used to determine serum TNF-α. IL-1β levels. Paired t test was used for statistical analysis. Results The HMGB1 expression was detectable at 2 hours after injection, which dramatically increased over time and peaked at 24 hours after injection. The serum TNF-a level and IL-1β level increased right after injection. The TNF-a level peaked at 8 hours after injection with a maximum value of （473.42±22. 99） pg/mL. The IL-1β level peaked at 2 hours after injection with a maximum value of （724. 49±34. 24） pg/mL. Both cytokine levels slowly decreased after peaking. IL-1β level returned normal with （51. 49±36. 87） pg/mL. Conclusions HMGB1 is one of the most important factors during the development of acute hepatic failure, which can promote the secretion of TNF-α and IL-1β at early stage and be abundantly expressed under the effect of these cytokines at middle and late stages with the result of liver damage. This process is directly correlated with the development and severity of hepatic failure.