Yumoto Miho, Nishida Osamu, Moriyama Kazuhiro, Shimomura Yasuyo, Nakamura Tomoyuki, Kuriyama Naohide, Hara Yoshitaka, Yamada Shingo
Department of Anesthesiology and Critical Care Medicine, Fujita Health University School of Medicine, Aichi, Japan.
Ther Apher Dial. 2011 Aug;15(4):385-93. doi: 10.1111/j.1744-9987.2011.00971.x.
The high mobility group box 1 protein (HMGB1) is an alarmin that plays an important role in sepsis and has been recognized as a promising target with a wide therapeutic window; however, no drugs and devices are currently in practical use. We hypothesized that hemofilters composed of porous membranes or cytokine-adsorbing membranes could remove HMGB1 from the blood. We performed experimental hemofiltration in vitro using four types of hemofilters composed of different membranes specifically designed for continuous hemofiltration. The test solution was a 1000-mL substitution fluid containing 100 µg of HMGB1 and 35 g of bovine serum albumin. Experimental hemofiltration was conducted for 360 min in a closed loop circulation system. Among the four membranes, surface-treated polyacrylonitrile (AN69ST) showed the highest capacity to adsorb HMGB1; it adsorbed nearly 100 µg of HMGB1 in the initial 60 min and showed a markedly high clearance rate (60.8 ± 5.0 mL/min) at 15 min. The polymethylmethacrylate membrane had half of the adsorption capacity of the AN69ST membrane. Although the highest sieving coefficient for HMGB1 was obtained with the high cut-off polyarylethersulfone membrane, which correlated with a constant filtrate clearance rate, albumin loss was observed. However, no such removal of both HMGB1 and albumin was observed with the polysulfone membrane and tubing. We conclude that continuous hemofiltration using the AN69ST membrane is a promising approach for HMGB1-related sepsis.
高迁移率族蛋白B1（HMGB1）是一种警报素，在脓毒症中起重要作用，并且已被认为是一个具有广阔治疗窗口的有前景的靶点；然而，目前尚无药物和设备投入实际使用。我们推测，由多孔膜或细胞因子吸附膜组成的血液滤过器可以从血液中清除HMGB1。我们使用四种由专门设计用于连续性血液滤过的不同膜组成的血液滤过器进行了体外实验性血液滤过。测试溶液是一种1000 mL的置换液，含有100 μg的HMGB1和35 g牛血清白蛋白。在闭环循环系统中进行360分钟的实验性血液滤过。在这四种膜中，表面处理的聚丙烯腈（AN69ST）显示出最高的吸附HMGB1的能力；它在最初60分钟内吸附了近100 μg的HMGB1，并且在15分钟时显示出明显较高的清除率（60.8±5.0 mL/分钟）。聚甲基丙烯酸甲酯膜的吸附能力是AN69ST膜的一半。尽管高截留聚芳醚砜膜对HMGB1的筛系数最高，这与恒定的滤液清除率相关，但观察到有白蛋白损失。然而，聚砜膜和管路未观察到同时清除HMGB1和白蛋白的情况。我们得出结论，使用AN69ST膜进行连续性血液滤过是治疗与HMGB1相关脓毒症的一种有前景的方法。
