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：在温暖的血心毛细血管上，在血液灌注的孤立的大鼠心脏中评估了补充siallyl lewis^x类似物，这是所有三个选择家庭成员的主要配体。我们评估了心肌和内皮功能的保存，并避免了凋亡。隔离的心被以20分钟的间隔给予温暖的血液心脏手术，将孤立的心脏逮捕60分钟。随后是60分钟的再灌注。根据添加到心骨溶液中的补充药物，将心脏分为以下两组。对照组（n = 10）接受了标准的温暖血液心脏。 SLX组（n = 10）接受了补充siallyl Lewis^x Abalogue（60μg/ml）的温暖血液心脏。心脏功能，内皮功能，心肌代谢和心肌肌过氧酶活性在心脏局部停滞之前和之后评估。组织变体…通过透射电子显微镜检查了更多的神学。通过DNA片段化和TUNEL确定凋亡。反应：在再灌注过程中，在SLX组中保留了比对照组更好的心脏功能。添加ACH时，SLX组的Flow和NO产品比对照组大。在心肌组织中的MPO，在SLX组中E-选择素和P-选择素的表达低于对照组。透射电子显微镜在对照组中显示出内皮细胞损伤和凋亡体的外观，而在SLX组中，这种形态学的变化较少。对照组显示了DNA梯子和TUNEL阳性细胞。结果表明，选择素介导的内皮 - 白细胞相互作用可能在心肌缺血和再灌注损伤中起重要作用。在温暖血液心脏方期间补充siAllyl Lewis^x类似物可以通过抑制白细胞 - 内皮相互作用并避免在早期再灌注期间避免心肌/内皮细胞凋亡来提供高级心肌保护。较少的