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

Abstract

AIM:

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.

METHODS:

Rats underwent partial hepatic ischemia followed by reperfusion, and changes in HMGB1 were assessed. Recombinant thrombomodulin was used as an inhibitor of HMGB1.

RESULTS:

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 24 h after surgery were significantly lower in the rTM(+) group than the rTM(-) group (P < 0.001). The plasma alanine aminotransferase level at 24 h 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 24 h after surgery was significantly smaller in the rTM(+) group than the rTM(-) group (P < 0.001).

CONCLUSIONS:

Recombinant thrombomodulin can serve as a treatment for I/R liver injury by inhibiting HMGB1.

• Authors: Koichi Kimura, Tomoharu Yoshizumi, Shoichi Inokuchi, Shinji Itoh, Takashi Motomura, Yohei Mano, Takeo Toshima, Noboru Harada, Norifumi Harimoto, Toru Ikegami, Yuji Soejima, Yoshihiko Maehara
• Journal: Hepatology research : the official journal of the Japan Society of Hepatology (Hepatol Res) Vol. 48 Issue 5 Pg. 391-396 (Apr 2018) ISSN: 1386-6346 [Print] Netherlands
• PMID: 29168258 (Publication Type: Journal Article)
• Copyright: © 2017 The Japan Society of Hepatology.