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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

目的：观察三种选择素家族成员的主要配体Sialyl Lewis^x类似物在离体大鼠血灌注心脏温血停跳时的作用。我们评估了心肌和内皮功能的保存，以及细胞凋亡的避免。方法：20只Wistar大鼠制备血灌注离体大鼠心脏模型。离体心脏停搏60分钟，每隔20分钟给予温血停搏。然后再灌注60分钟。根据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）采用标准温血停搏。SLX组（n=10）给予温血停搏液，加用Sialyl Lewis^x类似物（60 μg/ml）。测定心脏骤停前后的心功能、内皮功能、心肌代谢和心肌过氧化物酶活性。组织形态…更多形态学用透射电子显微镜检查。细胞凋亡通过DNA片段化和TUNEL检测。结果：SLX组在再灌注过程中心功能的保存优于对照组。SLX组的C.flow和NO prod均高于对照组。是补充道。SLX组心肌组织MPO、内皮组织e -选择素和p -选择素的表达均低于对照组。透射电镜显示对照组内皮细胞损伤，出现凋亡小体，而SLX组这种形态学改变较少。对照组呈DNA阶梯状，tunel阳性细胞。提示选择素介导的内皮-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。在温血心脏骤停期间补充Sialyl Lewis^x类似物可能通过抑制白细胞-内皮相互作用和避免心肌/内皮细胞凋亡在早期再灌注期间提供更好的心肌保护。少