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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进行组织移植和再植的难题。已有研究表明，在缺血再灌流过程中，白细胞和血管内皮细胞可释放多种炎症介质。选择素家族在炎症反应中起重要作用，参与炎症过程中激活的白细胞与血管内皮细胞的黏附。选择素家族包括LECAM-1、ELAM-1和P-选择素，它们在激活的血管内皮细胞中表达，并在白细胞与血管内皮细胞黏附时介导特殊的白细胞滚动现象。本研究的目的是评价抗LECAM-1、ELAM-1和P-选择素的单抗(MAb)对大鼠皮瓣白细胞-内皮细胞黏附的阻断作用，以预防大鼠皮肤I-R损伤。一种(45x30 Mm)…皮瓣单侧分离腹壁浅动脉供血较多，包括股血管。股血管夹闭上腹壁血管，缺血9h。治疗组动物静脉注射抗LECAM-1、ELAM-1和P-选择素的单抗。再灌流前15min；对照组给予生理盐水。通过描绘活体区域和非活体区域的轮廓来评估皮瓣的存活率。在接下来的7天内收集数据。结果：追踪分析显示，治疗组皮瓣平均存活面积约为80%，对照组约为20%(p&lt；0.05)。组织病理学观察，治疗组炎性改变不明显，而对照组损伤明显。结论：本研究结果表明，热缺血9h后，应用LECAM-1、ELAM-1和P-选择素的单抗治疗皮瓣I-R损伤是有效的。较少