REDUCTION OF ISCHEMIA-REPERFUSION INJURY TO SKIN FLAP MODEL BY MONOCLONAL ANTIBODY TO ADHESION MOLECULE-EXPERIMENTAL STUDY-

目的：缺血-再灌注（I-R）损伤仍然是长期缺血后自由组织移植和再植成功的一个问题。研究表明，白细胞和血管内皮细胞在缺血后的再灌注过程中释放多种炎症介质。血管细胞粘附分子-1 （vascular cell adhesion molecule-1, VCAM-1）是白细胞黏附受体的一种配体。本研究的目的是评价VCAM-1/VLA-4、他克莫司、LECAM-1单克隆抗体（MAb）阻断大鼠皮瓣白细胞内皮粘附对I-R损伤的影响。方法：雄性SD大鼠225 ~ 250gr。单侧分离由上腹部浅A&V（包括股血管）提供的皮瓣（45×30mm）。将股血管与腹壁血管交叉夹持，缺血9小时。治疗组动物在再灌注前15分钟给予VCAM-1/VLA-4、他克莫司、LECAM-1单抗；对照组给予生理盐水治疗。通过追踪活区和非活区轮廓来评估皮瓣的生存能力。在接下来的7天收集数据。这些数据与皮瓣类似区域的组织学证据相证实。结果：示踪分析显示，治疗组皮瓣平均存活面积约为70%，对照组约为20% （p<0.05）。组织病理学上，治疗组未见明显炎症改变，对照组损伤明显。结论：在本研究中，我们得出用单抗治疗VCAM-1、他克莫司、LECAM-1的皮瓣对热缺血后9小时的I-R损伤有效。

Aim : Ischemia-reperfusion(I-R) injury continues to be a problem for successful free tissue transfer and replantation after prolonged periods of ischemia. It has been shown that leukocytes and vascular endothelial cells release a variety of inflammatory mediators during reperfusion after ischemia. The vascular cell adhesion molecule-1 (VCAM-1) is a ligand on the endothelium for some of the adhesion receptors on leukocytes. The purpose of this study was to evaluate the blockage of leukocyte-endothelial adhesion by a monoclonal antibody (MAb) to VCAM-1/VLA-4, Tacrolimus, LECAM-1 in skin flaps to prevent I-R injury in rats.Methods : Male SD rats (225-250gr) were used. A skin flap (45×30mm) supplied by the superficial epigastric A&V including the femoral vessels was isolated unilaterally. The femoral vessels were cross-clamped the epigastric vessels for 9 hours of ischemia. Animals in treated group received MAb to VCAM-1/VLA-4, Tacrolimus, LECAM-1 i.v. 15 minutes prior to reperfusion ; those in the control group received normal saline. Skin flap viability was assessed by tracing the outline of viable and nonviable areas. Data were collected for the following 7 days. These data were corroborated with histological evidence on comparable areas of the flap.Results : Tracing analysis revealed average flap survival area of about 70% in treated group and about 20% in control group (p<0.05). Histopathologically, few inflammatory changes could be observed in treated group, while marked damage was observed in control group.Conclusions : From this study, we concluded that treating skin flaps with Mab to VCAM-1, Tacrolimus, LECAM-1 was effective for I-R injury after 9 hours of warm ischemia.