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Inhibitory effects of Sialyl Lewis^x oligosaccharide on reperfusion injury by avoidance of apoptosis

Sialyl Lewis^x 寡糖通过避免细胞凋亡对再灌注损伤的抑制作用

基本信息

批准号：
15591505
负责人：
HAYASHIDA Nobuhiko
金额：
$ 1.73万
依托单位：
KURUME 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 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15591505/
关键词：
apoptosis Sialyl Lewis^x reperfusion injury endothelial function myocardial metabolism 血管内皮細胞

项目摘要

Object : Effects of supplemental Sialyl Lewis^x analogue, a major ligand for all three selectin family members, during warm blood cardioplegia were assessed in the blood perfused isolated rat heart. We evaluated the preservation of myocardial and endothelial function, and the avoidance of apoptosis.Method : The blood-perfused isolated rat heart model was prepared with 20 Wistar rats. The isolated hearts were arrested for 60 min with warm blood cardioplegia given at 20-min intervals. This was followed by 60 min of reperfusion. The hearts were divided into the following two groups according to the supplemental drugs added to the cardioplegic solution. The control group (n=10) received standard warm blood cardioplegia. The SLX group (n=10) received warm blood cardioplegia supplemented with Sialyl Lewis^x analogue (60 μg/ml). Cardiac function, endothelial function, myocardial metabolism and myocardial myeroperoxidase activity were assessed before and after cardioplegic arrest. Tissue morph … More ology was examined by transmission electron microscopy. Apoptosis was determined by DNA fragmentation and TUNEL.Result : Cardiac function was preserved better in the SLX group than the control group during reperfusion. C.flow and NO prod were greater in the SLX group than the control group when Ach.was added. MPO in myocardial tissue, expression of E-selectin and P-selectin in endthelium were lower in the SLX group than the control group. Transmission electron microscopy showed endothelial cell damage and appearance of apoptosis body in the control group, whereas such morphological change was less in the SLX group. DNA ladder and TUNEL-positive cell was shown in the control group. The results suggest that selectin-mediated endothelial-leukocyte interactions may play an important role in myocardial ischemia and reperfusion injury. Supplementation of Sialyl Lewis^x analogue during warm blood cardioplegia may provide superior myocardial protection by suppressing leukocyte-endothelial interaction and the avoidance of myocardial/endothelial apoptosis during early reperfusion period. Less

对象：在血液灌注的离体大鼠心脏中，评估了在温血心脏停搏期间补充Sialyl刘易斯^x类似物（所有三种选择素家族成员的主要配体）的作用。方法：用20只Wistar大鼠建立离体心脏血液灌流模型，观察其对心肌和内皮细胞功能的保护作用。离体心脏停搏60 min，每隔20 min灌注一次温血停搏液。然后再灌注60分钟。根据心脏停搏液中添加的补充药物将心脏分为以下两组。对照组（n=10）给予标准温血停搏液。SLX组（n=10）给予含Sialyl刘易斯^x类似物（60 μg/ml）的温血停搏液。观察停搏前后心功能、内皮功能、心肌代谢和心肌过氧化物酶活性的变化。组织形态 ...更多信息通过透射电子显微镜检查组织学。结果：与对照组相比，SLX组在再灌注过程中心脏功能的保护作用更好。加入Ach后，SLX组的C.flow和NO产生量均高于对照组。SLX组心肌组织MPO、E-选择素、P-选择素表达均低于对照组。透射电镜观察显示对照组内皮细胞损伤，出现凋亡小体，而SLX组内皮细胞损伤较轻。对照组可见DNA梯状条带和TUNEL阳性细胞。结果提示，选择素介导的内皮细胞-白细胞相互作用可能在心肌缺血再灌注损伤中起重要作用。在温血停搏液中补充Sialyl刘易斯^x类似物可能通过抑制白细胞-内皮细胞相互作用和避免再灌注早期心肌/内皮细胞凋亡而提供上级心肌保护。少