Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
Dig Dis Sci. 2010 Mar;55(3):596-606. doi: 10.1007/s10620-009-0768-6. Epub 2009 Mar 4.
While several clinical trials have suggested that leukocytapheresis (LCAP) by filtration can benefit patients with active ulcerative colitis, the mechanisms underlying these benefits are largely unknown. The aim of this study was to address the mechanisms that may underlie the therapeutic effects of LCAP using a dextran sulfate sodium-induced colitis model in rats. Treatment with the active column, but not the sham column, improved disease severity by down-regulating pro-inflammatory events, including the cell-proliferative responses and inflammatory cytokine and reactive oxygen production, as well as by up-regulating protective events, including hepatocyte growth factor production, bone marrow-derived endothelial progenitor cell induction, and colonic blood flow levels, which were mediated predominantly by calcitonin gene-related peptide. The improvement was also associated with the increase of Ki-67 labeling in the colonic epithelium. In conclusion, the LCAP procedure was used in a dextran sulfate sodium-induced colitis model in rats under extracorporeal circulation conditions. This approach down-regulated pro-inflammatory events and up-regulated protective events in association with disease improvement. These data suggest that LCAP is feasible in animals and should shed light on the mechanisms of LCAP in clinical settings.
虽然几项临床试验表明，通过过滤进行白细胞吸附（LCAP）可以使活动性溃疡性结肠炎患者受益，但这些益处的机制在很大程度上尚不清楚。本研究旨在使用葡聚糖硫酸钠诱导的大鼠结肠炎模型来解决 LCAP 治疗效果的可能机制。用活性柱（而非假柱）处理可通过下调促炎事件（包括细胞增殖反应和炎性细胞因子及活性氧产生）来改善疾病严重程度，并通过上调保护事件（包括肝细胞生长因子产生、骨髓来源的内皮祖细胞诱导和结肠血流水平）来改善疾病严重程度，这些事件主要由降钙素基因相关肽介导。改善与结肠上皮中的 Ki-67 标记物增加有关。总之，在体外循环条件下，将 LCAP 程序用于葡聚糖硫酸钠诱导的大鼠结肠炎模型。这种方法可下调促炎事件，并上调保护事件，从而改善疾病。这些数据表明 LCAP 在动物中是可行的，应该为临床环境中的 LCAP 机制提供一些启示。
