Rubio-Avilla J, Palma-Vargas J M, Collins J T, Smejkal R, McLaren J, Phillips L M, Toledo-Pereyra L H
The Surgical Research Institute and Trauma Division at Borgess Medical Center, Kalamazoo, Michigan 49001, USA.
J Trauma. 1997 Aug;43(2):313-8. doi: 10.1097/00005373-199708000-00017.
Little is known about the changes in the hepatic microcirculation and the leukocyte-endothelial adhesion processes during the early reperfusion period after resuscitation in hemorrhagic shock. P-selectin and its natural ligand Sialyl Lewis(x) (SLe(x)) are involved in the early stages of reperfusion events leading to neutrophil migration. Therefore, the aim of this study was to investigate the effect of the administration of CY-1503 [corrected], a synthetic SLe(x) analog, in the liver inflammatory response and neutrophil migration after hemorrhagic shock.
Rats, each weighing 275 to 300 grams, were subjected to 60 minutes of pressure controlled hemorrhagic shock. After this period, animals were resuscitated according to the following protocol: shed blood was reinfused to equal 50% of the total volume bled, and the other 50% was replaced with 3x volume of Ringer's lactated solution. Animals were divided into sham and two study groups to receive vehicle (controls) and CY-1503 [corrected] (10 mg/kg intravenously) diluted in 1 mL of normal saline 45 minutes after initiating hemorrhagic shock. The following parameters were analyzed: 7-day survival, liver injury tests, liver tissue myeloperoxidase as an index of neutrophil infiltration, and liver histology.
Survival was significantly increased from 48% in the controls to 90% in the CY-1503 [corrected] treated group. Animals treated with the SLe(x) analog showed significantly better mean arterial blood pressure after 15 minutes after resuscitation. Also, the treated group showed a marked decrease in liver enzymes levels at 5 minutes and 4 hours after reperfusion. Neutrophil migration was significantly ameliorated as reflected by decreased myeloperoxidase levels in the SLe(x) analog treated group. Furthermore, we observed improved histologic damage scores in the treated group when compared with controls.
The SLe(x) analog, CY-1503 [corrected], had a protective effect in ischemic livers by decreasing neutrophil migration after hemorrhagic shock and resuscitation. This protective effect also resulted in improved survival and mean arterial blood pressure after resuscitation.
关于失血性休克复苏后早期再灌注期间肝微循环变化以及白细胞 - 内皮细胞黏附过程，人们了解甚少。P - 选择素及其天然配体唾液酸化路易斯寡糖（SLe(x)）参与导致中性粒细胞迁移的再灌注事件早期阶段。因此，本研究旨在探讨给予合成SLe(x)类似物CY - 1503在失血性休克后肝脏炎症反应和中性粒细胞迁移中的作用。
体重275至300克的大鼠接受60分钟的压力控制失血性休克。在此期间后，动物按以下方案复苏：回输失血量的50%，其余50%用3倍体积的乳酸林格氏液替代。动物分为假手术组和两个研究组，在失血性休克开始45分钟后，分别接受载体（对照组）和稀释于1毫升生理盐水中的CY - 1503（10毫克/千克静脉注射）。分析以下参数：7天生存率、肝损伤检测、作为中性粒细胞浸润指标的肝组织髓过氧化物酶以及肝脏组织学。
生存率从对照组的48%显著提高至CY - 1503治疗组的90%。用SLe(x)类似物治疗的动物在复苏后15分钟时平均动脉血压显著更好。此外，治疗组在再灌注后5分钟和4小时时肝酶水平显著降低。SLe(x)类似物治疗组髓过氧化物酶水平降低，反映中性粒细胞迁移显著改善。此外，与对照组相比，我们观察到治疗组的组织学损伤评分有所改善。
SLe(x)类似物CY - 1503通过减少失血性休克和复苏后中性粒细胞迁移，对缺血肝脏具有保护作用。这种保护作用还导致复苏后生存率提高和平均动脉血压改善。
