Hemoperfusion with a high-mobility group box 1 adsorption column can prevent the occurrence of hepatic ischemia-reperfusion injury in rats.
OBJECTIVE
High-mobility group box 1, a ubiquitous nonhistone chromosomal protein, is passively released from necrotic cells and actively secreted by inflammatory cells. Extracellular high-mobility group box 1 has recently been recognized to be a mediator of hepatic ischemia-reperfusion injury; however, the kinetics of high-mobility group box 1 during hepatic ischemia-reperfusion and the role of high-mobility group box 1 in ischemia-reperfusion injury still remain poorly understood. This study was designed to assess the localization and the kinetics of high-mobility group box 1 during hepatic ischemia-reperfusion injury and the effects of high-mobility group box 1 adsorption column in hepatic ischemia-reperfusion injury.


METHODS
A prospective, randomized animal study.


METHODS
University medical center research laboratory.


METHODS
Male Sprague-Dawley rats.


METHODS
The animals underwent 70% partial hepatic ischemia for 60 or 90 mins and were then reperfused. To investigate the high-mobility group box 1 levels in the serum and in the liver, the animals were killed at predetermined periods. As a lethal model, global hepatic ischemia-reperfusion was induced by portal triad cross-clamping for 30 mins. Hemoperfusion therapy using a cellulofine sulfate bead column (high-mobility group box 1 adsorption column) was performed during global hepatic ischemia.


RESULTS
During 60 mins of 70% hepatic ischemia, nuclear high-mobility group box 1 was translocated to the cytoplasm in hepatocytes; however, serum high-mobility group box 1was not increased. Immediately after reperfusion, the serum high-mobility group box 1 was significantly increased (p < .05). High-mobility group box 1 mediated ischemia-reperfusion injury in not only liver but also the remote organ, lung. Removal of excess high-mobility group box 1 in blood using an adsorption column significantly improved animal survival (p < .03) and liver and lung injuries.


CONCLUSIONS
High-mobility group box 1 plays an important role in the systemic as well as local pathogenesis of hepatic ischemia-reperfusion injury. The removal of excessive high-mobility group box 1 with adsorption column was beneficial and promising option in ischemia-related liver injuries.
Yamamoto
Tetsu
T
Department of Digestive and General Surgery, Faculty of Medicine, Shimane University, Izumo, Japan.
Ono
Takashi
T
Ito
Takashi
T
Yamanoi
Akira
A
Maruyama
Ikuro
I
Tanaka
Tsuneo
T
D000818:Animals; D024243:HMGB1 Protein / Q000032:analysis / Q000502:physiology*; D006464:Hemoperfusion / Q000379:methods*; D007124:Immunoenzyme Techniques; D007700:Kinetics; D008099:Liver / Q000098:blood supply* / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy
D024243:HMGB1 Protein; C104200:Hbp1 protein, rat