中文摘要：

目的 探索重组血栓调节蛋白N端结构域（rTM-N）和可溶性晚期糖化终末产物受体（rsRAGE）对急性肝衰竭模型小鼠的保护作用. 方法 原核表达、纯化得到rTM-N和rsRAGE,腹腔注射rTM-N或rsRAGE至急性肝衰竭模型小鼠,用不同方法检测肝组织高迁移族蛋白（HMG） B1及核因子-κ B的表达水平、血清中肿瘤坏死因子α和白细胞介素1 β的含量.对数据进行单因素方差分析. 结果 成功表达并纯化rTM-N和rsRAGE,相对分子质量约为1600和31600.各实验组小鼠肝组织坏死情况明显好转,免疫组织化学检测显示,HMGB1表达水平在实验1组和实验2组明显低于对照组；免疫荧光检测核因子-κB的表达水平,在实验1组和实验2组也明显低于对照组.RT-PCR检测HMGB1 mRNA显示,实验1组峰值（114.99±6.53）和实验2组峰值（98.44±13.69）明显低于对照组峰值（199.30±11.51）,差异有统计学意义（P＜0.05）.血清肿瘤坏死因子α在实验1组12h的峰值为（355.42±53.55）pg/ml、实验2组12h的峰值为（451.15±79.66）pg/ml,也显著低于对照组6h的峰值（634.23±35.18）pg/ml,差异有统计学意义（F=109.31,P＜0.05）.血清白细胞介素1 β在实验l组的峰值（457.32±34.99） pg/ml和实验2组的峰值（530.66±38.83）pg/ml显著低于对照组在6h达到的峰值（688.91±48.27） pg/ml,差异有统计学意义（F=65.48,P＜0.05）.结论 rsRAGE和rTM-N均可显著减少急性肝衰竭模型小鼠肝组织HMGB1的表达水平,显示对急性肝衰竭鼠较强的保护作用.

英文摘要：

Objective To evaluate the roles of N-terminal lectin-like domain of thrombomodulin （TM-N） and receptor for advanced glycation end products （RAGE） in acute hepatic failure using a mouse model system.Methods Acute hepatic failure was induced in Kunming mice by intraperitonenl injection of D-galactosamine （D-Galn at 600 mg/kg） and lipopolysaccharide （LPS at 5 μg/kg） and mice were divided into groups for injection with saline,recombinant （r）TM-N protein,or recombinant soluble （rs）RAGE protein.Unmanipulated model mice served as the negative controls.Effects on liver expression of high mobility group box-1 （HMGB1） were detected by immunohistochemistry and real time RT-PCR.Effects on serum levels of tumor necrosis factor-alpha （TNFα） and interleukin-1 beta （IL）-1b were quantified by ELISA.Results Treatment with rTM-N and rsRAGE both alleviated the acute liver damage induced by D-Galn/LPS exposure,and decreased the hepatic expression of HMGB1 as well as the serum levels of TNFα and IL-1b.Conclusion Intraperitoneal delivery of rTM-N and rsRAGE can alleviate acute liver damage by modulating the expression of necrosis-and inflammatión-related factors.