Department of Digestive and General Surgery, Faculty of Medicine, Shimane University, Izumo, Japan.
Crit Care Med. 2010 Mar;38(3):879-85. doi: 10.1097/CCM.0b013e3181c58951.
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.
A prospective, randomized animal study.
University medical center research laboratory.
Male Sprague-Dawley rats.
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.
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.
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.
高迁移率族蛋白 B1 是一种普遍存在的非组蛋白染色体蛋白，它可以从坏死细胞中被动释放，并由炎症细胞主动分泌。细胞外高迁移率族蛋白 B1 最近被认为是肝缺血再灌注损伤的介质；然而，肝缺血再灌注过程中高迁移率族蛋白 B1 的动力学以及高迁移率族蛋白 B1 在缺血再灌注损伤中的作用仍知之甚少。本研究旨在评估肝缺血再灌注损伤过程中高迁移率族蛋白 B1 的定位和动力学，并研究高迁移率族蛋白 B1 吸附柱在肝缺血再灌注损伤中的作用。
一项前瞻性、随机动物研究。
大学医学中心研究实验室。
雄性 Sprague-Dawley 大鼠。
动物接受 70%的部分肝缺血 60 或 90 分钟，然后再灌注。为了研究血清和肝脏中高迁移率族蛋白 B1 的水平，动物在预定的时间点被处死。作为一个致死模型，通过门静脉三联夹闭诱导 30 分钟的全肝缺血再灌注。在全肝缺血期间，使用纤维素硫酸珠柱（高迁移率族蛋白 B1 吸附柱）进行血液灌流治疗。
在 70%肝缺血 60 分钟期间，核高迁移率族蛋白 B1 向肝细胞胞浆转位；然而，血清高迁移率族蛋白 B1 没有增加。再灌注后即刻，血清高迁移率族蛋白 B1 明显增加（p <.05）。高迁移率族蛋白 B1 不仅介导肝缺血再灌注损伤，还介导远隔器官肺的损伤。使用吸附柱从血液中去除过多的高迁移率族蛋白 B1 显著提高了动物的存活率（p <.03）和肝肺损伤。
高迁移率族蛋白 B1 在肝缺血再灌注损伤的全身和局部发病机制中发挥重要作用。使用吸附柱去除过多的高迁移率族蛋白 B1 是一种有益且有前途的缺血相关肝损伤治疗选择。
