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Potential effect of recombinant thrombomodulin on ischemia–reperfusion liver injury in rats
Author(s) -
Kimura Koichi,
Yoshizumi Tomoharu,
Inokuchi Shoichi,
Itoh Shinji,
Motomura Takashi,
Mano Yohei,
Toshima Takeo,
Harada Noboru,
Harimoto Norifumi,
Ikegami Toru,
Soejima Yuji,
Maehara Yoshihiko
Publication year - 2018
Publication title -
hepatology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.123
H-Index - 75
eISSN - 1872-034X
pISSN - 1386-6346
DOI - 10.1111/hepr.13005
Subject(s) - thrombomodulin , recombinant dna , medicine , ischemia , reperfusion injury , cardiology , chemistry , biochemistry , gene , platelet , thrombin
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.