Hemoperfusion with a high-mobility group box 1 adsorption column can prevent the occurrence of hepatic ischemia-reperfusion injury in rats

作者：Yamamoto Tetsu^*; Ono Takashi; Ito Takashi; Yamanoi Akira; Maruyama Ikuro; Tanaka Tsuneo

来源：Critical Care Medicine, 2010, 38(3): 879-885.

DOI：10.1097/CCM.0b013e3181c58951

• high-mobility group box 1 adsorption column
• ischemia-reperfusion injury
• liver
• hemoperfusion
• neutralization antibody

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.
Design: A prospective, randomized animal study.
Setting: University medical center research laboratory.
Subjects: Male Sprague-Dawley rats.
Investigation: 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.
Measurements and Main 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 1 was 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. (Crit Care Med 2010; 38: 879-885)

• 出版日期2010-3