Protective effect of recombinant TM-N and recombinant soluble RAGE in a mouse model of acute hepatic failure / 中华肝脏病杂志

ABSTRACT

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>Acute hepatic failure was induced in Kunming mice by intraperitoneal injection of D-galactosamine (D-Galn at 600 mg/kg) and lipopolysaccharide (LPS at 5 mug/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 (TNFa) and interleukin-1 beta (IL)-1b were quantified by ELISA.</p><p><b>RESULTS</b>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 TNFa and IL-1b.</p><p><b>CONCLUSION</b>Intraperitoneal delivery of rTM-N and rsRAGE can alleviate acute liver damage by modulating the expression of necrosis- and inflammation-related factors.</p>