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

粘附分子单克隆抗体减少皮瓣模型缺血再灌注损伤的实验研究。

基本信息

批准号：
15591901
负责人：
TOSA Yasuyoshi
金额：
$ 2.18万
依托单位：
SHOWA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2006
项目状态：
已结题

项目摘要

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 selectin family, which mediates adhesion of activated leukocytes and vascular endothelium in inflammation at lesion sites, is considered to play an important role in the sequence of inflammatory reactions. The selectin family includes LECAM-1, ELAM-1, and P-selectin, which are expressed in activated vascular endothelium and mediates the special leukocyte rolling phenomenon seen when leukocytes adhere to vascular endothelium. The purpose of this study was to evaluate the blockage of leukocyte-endothelial adhesion by a monoclonal antibody (MAb) to LECAM-1, ELAM-1, and P-selectin in skin flaps to prevent I-R injury in rats.Methods : Male SD rats (225-250gr) were used. A skin flap (45x30mm) … More 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 LECAM-1, ELAM-1, and P-selectin 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 80% 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 LECAM-1, ELAM-1, and P-selectin were effective for I-R injury after 9 hours of warm ischemia. Less

目的：缺血-再灌注（I-R）损伤仍然是长时间缺血后成功的游离组织移植和再植的问题。研究表明，在缺血再灌注过程中，白细胞和血管内皮细胞释放多种炎症介质。选择素家族介导炎症反应中活化的白细胞与血管内皮细胞的粘附，在炎症反应的发生顺序中起重要作用。选择素家族包括LECAM-1、ELAM-1和P-选择素，它们在活化的血管内皮中表达，并介导当白细胞粘附于血管内皮时所见的特殊白细胞滚动现象。本研究的目的是评价LECAM-1、ELAM-1和P-选择素的单克隆抗体（MAb）阻断皮瓣中白细胞-内皮细胞粘附以预防大鼠I-R损伤。皮瓣（45 x30 mm） ...更多信息单侧分离由包括股血管在内的上腹浅动静脉供应的血管。将股血管与上腹部血管交叉夹闭缺血9小时。治疗组于再灌注前15 min静脉注射抗LECAM-1、ELAM-1和P-选择素单克隆抗体，对照组注射生理盐水。通过追踪存活和非存活区域的轮廓来评估皮瓣的存活能力。在接下来的7天内收集数据。结果：追踪分析显示，治疗组皮瓣平均成活面积约为80%，对照组约为20%（P<0.05）。从组织学上看，治疗组中可以观察到一些炎症变化，而对照组中观察到明显的损伤。结论：从这项研究中，我们得出结论，治疗皮瓣与单抗LECAM-1，ELAM-1，和P-选择素是有效的I-R损伤后9小时的热缺血。少