Nishiyama R, Shinoda M, Tanabe M, Oshima G, Takano K, Miyasho T, Fuchimoto Y, Yamada S, Inoue T, Shimada K, Suda K, Tanaka M, Hayashida T, Yagi H, Kitago M, Obara H, Itano O, Takeuchi H, Kawachi S, Maruyama I, Kitagawa Y
Department of Surgery, Keio University School of Medicine, Tokyo, Japan.
Eur Surg Res. 2013;51(3-4):181-90. doi: 10.1159/000357563. Epub 2014 Jan 9.
High-mobility group box chromosomal protein 1 (HMGB1) has recently been identified as an important mediator of various kinds of acute and chronic inflammation. A method for efficiently removing HMGB1 from the systemic circulation could be a promising therapy for HMGB1-mediated inflammatory diseases.
In this study, we produced a new adsorbent material by chemically treating polystyrene fiber. We first determined whether the adsorbent material efficiently adsorbed HMGB1 in vitro using a bovine HMGB1 solution and a plasma sample from a swine model of acute liver failure. We then constructed a column by embedding fabric sheets of the newly developed fibers into a cartridge and tested the ability of the column to reduce plasma HMGB1 levels during a 4-hour extracorporeal hemoperfusion in a swine model of acute liver failure.
The in vitro adsorption test of the new fiber showed high performance for HMGB1 adsorption (96% adsorption in the bovine HMGB1 solution and 94% in the acute liver failure swine plasma, 2 h incubation at 37°C; p < 0.05 vs. incubation with no adsorbent). In the in vivo study, the ratio of the HMGB1 concentration at the outlet versus the inlet of the column was significantly lower in swine hemoperfused with the newly developed column (53 and 61% at the beginning and end of perfusion, respectively) than in those animals hemoperfused with the control column (94 and 93% at the beginning and end of perfusion, respectively; p < 0.05). Moreover, the normalized plasma level of HMGB1 was significantly lower during perfusion with the new column than with the control column (p < 0.05 at 1, 2, and 3 h after initiation of perfusion).
These data suggest that the newly developed column has the potential to effectively adsorb HMGB1 during hemoperfusion in swine.
高迁移率族蛋白B1（HMGB1）最近被确定为各种急慢性炎症的重要介质。一种从体循环中有效去除HMGB1的方法可能是治疗HMGB1介导的炎症性疾病的一种有前景的疗法。
在本研究中，我们通过化学处理聚苯乙烯纤维制备了一种新型吸附材料。我们首先使用牛HMGB1溶液和急性肝衰竭猪模型的血浆样本，在体外确定该吸附材料是否能有效吸附HMGB1。然后，我们将新开发的纤维织物片嵌入柱芯构建了一个柱体，并在急性肝衰竭猪模型的4小时体外血液灌流过程中测试了该柱体降低血浆HMGB1水平的能力。
新纤维的体外吸附试验显示其对HMGB1具有高效吸附性能（在牛HMGB1溶液中吸附率为96%，在急性肝衰竭猪血浆中吸附率为94%，37°C孵育2小时；与无吸附剂孵育相比，p < 0.05）。在体内研究中，用新开发的柱体进行血液灌流的猪，柱体出口处与入口处的HMGB1浓度比显著低于用对照柱体进行血液灌流的猪（灌流开始时和结束时分别为53%和61%）（灌流开始时和结束时分别为94%和93%；p < 0.05）。此外，在使用新柱体灌流期间，HMGB1的标准化血浆水平显著低于使用对照柱体灌流时（灌流开始后1、2和3小时，p < 0.05）。
这些数据表明，新开发的柱体在猪血液灌流过程中具有有效吸附HMGB1的潜力。
