Potential effect of recombinant thrombomodulin on ischemia-reperfusion liver injury in rats.

Abstract

Liver ischemia-reperfusion (I/R) injury is a severe complication of liver surgery. However, the responsible molecular mechanism remains unclear. High-mobility group box 1 (HMGB1) is released from the nuclei of cells and behaves as a damage-associated molecular pattern. The aim of this study is to reveal the roles of HMGB1 and the effects of recombinant thrombomodulin (rTM) in I/R liver injury. Rats underwent partial hepatic ischemia followed by reperfusion, and changes in HMGB1 were assessed. Recombinant thrombomodulin was used as an inhibitor of HMGB1. In rats with I/R injury, the HMGB1 level significantly decreased in the liver tissue and significantly increased in the serum after surgery (P < 0.001 for both). No difference in the HMGB1 level in the hepatocytes was observed between the rTM(-) group and rTM(+) group after surgery. Conversely, the serum HMGB1 level was significantly lower in the rTM(+) group than the rTM(-) group after surgery (P < 0.001). The levels of tumor necrosis factor-α and interleukin-6 in the liver tissue 24h after surgery were significantly lower in the rTM(+) group than the rTM(-) group (P < 0.001). The plasma alanine aminotransferase level at 24h after surgery of the rTM(+) group was significantly decreased after surgery compared with that of the rTM(-) group (P < 0.001). The necrotic area of the liver tissue 24h after surgery was significantly smaller in the rTM(+) group than the rTM(-) group (P < 0.001). Recombinant thrombomodulin can serve as a treatment for I/R liver injury by inhibiting HMGB1.