Keck Tobias, Werner Jen, Schneider Lutz, Gebhard Martha-Maria, Klar Erns
Department of General and Digestive Surgery, University of Freiburg, Germany.
Surgery. 2003 Jul;134(1):63-71. doi: 10.1067/msy.2003.187.
Reperfusion injury contributes to early organ malfunction after transplantation. The aim of this study was to characterize the ischemia-reperfusion injury after pancreas transplantation and to evaluate the effect of monoclonal antibody therapy against ICAM-1.
Twenty-five heterotopic pancreas transplantations were performed in syngenic rats in a no-touch technique. Microcirculation and leukocyte-endothelial interaction in the grafts were evaluated by intravital microscopy at 1 hour (I), 6 hours (II), 12 hours (III), and 24 hours (IV) after reperfusion, and 12 hours after reperfusion (V) in the therapeutic group. In (V) antibodies against ICAM-1 were applied as bolus at reperfusion and continuously for 6 hours. Next to intravital microscopy, histologic scores, myeloperoxidase levels, and ICAM-1 expression were determined.
Microcirculation was significantly reduced in capillaries and postcapillary venules in the time course after reperfusion (capillary: 0.96 +/- 0.08 mm/s [I] to 0.45 +/- 0.07 mm/s [IV] [P <.01]) and was improved significantly by therapy with ICAM-1 antibodies (0.98 +/- 0.06 mm/s, (P <.01). Leukocyte-endothelial interaction significantly increased 6 hours after reperfusion (II) (P <.01). These changes were paralleled by an increased endothelial expression of ICAM-1 in immunohistochemistry. Histologic evaluation showed increased inflammation at 12 hours after reperfusion (P <.01), which could be diminished by the administration of ICAM-1 antibodies (P <.05).
Increased endothelial expression of ICAM-1 after pancreas transplantation is positively correlated with microcirculatory impairment. Important steps of pancreatic inflammation take place approximately 6 hours after reperfusion. Prophylactic application of monoclonal antibodies against ICAM-1 reduces reperfusion injury and successfully prevents the occurrence of graft pancreatitis.
再灌注损伤会导致移植术后早期器官功能障碍。本研究的目的是描述胰腺移植后的缺血再灌注损伤，并评估抗细胞间黏附分子-1（ICAM-1）单克隆抗体治疗的效果。
采用非接触技术在同基因大鼠中进行了25例异位胰腺移植。在再灌注后1小时（I）、6小时（II）、12小时（III）和24小时（IV），以及治疗组再灌注后12小时（V），通过活体显微镜评估移植物中的微循环和白细胞-内皮细胞相互作用。在（V）中，抗ICAM-1抗体在再灌注时作为推注给药，并持续6小时。除活体显微镜检查外，还测定了组织学评分、髓过氧化物酶水平和ICAM-1表达。
再灌注后的时间进程中，毛细血管和毛细血管后微静脉中的微循环显著减少（毛细血管：0.96±0.08mm/s[I]至0.45±0.07mm/s[IV][P<.01]），而ICAM-1抗体治疗可显著改善微循环（0.98±0.06mm/s，[P<.01]）。再灌注6小时后（II）白细胞-内皮细胞相互作用显著增加（P<.01）。免疫组织化学显示，这些变化与ICAM-1在内皮细胞中的表达增加平行。组织学评估显示，再灌注后12小时炎症增加（P<.01），而给予ICAM-1抗体可减轻炎症（P<.05）。
胰腺移植后内皮细胞ICAM-1表达增加与微循环障碍呈正相关。胰腺炎症的重要阶段大约在再灌注后6小时发生。预防性应用抗ICAM-1单克隆抗体可减少再灌注损伤，并成功预防移植胰腺胰腺炎的发生。
