肠缺血-再灌注损伤对中性粒细胞和内皮细胞粘附分子表达的影响及其与脏器损伤的关系

The relationship between expression of adhesion molecules on endothelial cells,polymorphonuclear leukocytes and remote organ dysfunction after gut ischemiareperfusion injury

目的：研究肠缺血再灌注过程对局部及远隔器官中性粒细胞（ＰＭＮ）和组织血管内皮细胞粘附分子表达的影响及其与脏器功能受损的关系。方法：雄性Ｗｉｓｔａｒ大白鼠，随机分为对照组、肠缺血组和再灌注组。比较肠缺血再灌注过程中局部及远隔器官组织髓过氧化物酶（ＭＰＯ）活性、ＰＭＮ上的配基ＣＤ１１ｂ／ＣＤ１８表达、细胞间粘附分子１（ＩＣＡＭ１）表达的变化以及主要脏器功能的改变。结果：①主要脏器功能变化异常的峰值均在再灌注后１小时～２小时，与组织ＭＰＯ活性升高的峰值时相基本一致；②再灌注１小时和２小时血清可刺激ＰＭＮ上ＣＤ１１ｂ／ＣＤ１８表达上调，与肺组织ＭＰＯ活性呈正相关关系；③肠缺血期，肠局部ＩＣＡＭ１ｍＲＮＡ表达有所增加，肠缺血及再灌注早期蛋白水平表达增加；肝及肺组织ＩＣＡＭ１ｍＲＮＡ表达有所增加，肠缺血及再灌注早期蛋白水平表达增加；肝及肺组织ＩＣＡＭ１ｍＲＮＡ表达及血管内皮细胞ＩＣＡＭ１分布在再灌注后的２小时和６小时增加。结论：缺血再灌注后肠血管可能作为“预激床”激活循环中ＰＭＮ，从而构成再灌注后ＰＭＮ在远隔器官聚集、活化，造成组织损伤的病理生理学基础；ＰＭＮ上ＣＤ１１ｂ／ＣＤ１８及血管内皮细胞上ＩＣＡＭ１表达上调则构?

Objective:To explore the molecular mechanisms underlying polymorphonuclear leukocytes (PMN) aggregation and activation in local and remote organs following gut ischemiareperfusion (GIR),and the relationship between activated PMN and organ dysfunction.Methods:Male Wistar rats were subjected to superior mesenteric artery occlusion followed by reperfusion.Animals were randomly divided into shamoperation,gut ischemia,gut ischemia and subsequent reperfusion groups.Tissue MPO activities,the expression of CD11b/CD18 on PMN and intercellular adhesion molecule1 ( ICAM1 ) on endothelial cells,and organ function parameters were determined.Results:①GIR resulted in remote organ dysfunction,and the most obvious abnormalities were parallel to the peak levels of tissue MPO activites.②In in vitro experiments,it showed that serum obtained at 1 hour and 2 hours postreperfusion could stimulate the expression of CD11b/CD18 on PMN,which positively correlated to increased MPO activities in liver and lungs.③The elevated ICAM1 expression was detected in gut vascular endothelial cells during ischemic stage and in liver and lungs during reperfusion stage,which was consistent with increased MPO activities in tissues.Conclusions:The intestinal blood vessel associated with GIR might serve as the “bed” for priming PMN,thereby resulting in the aggregation and activation of PMN in tissues,ending in inducing organ damage or dysfunction.The upregulation of CD11b/CD18 on PMN and ICAM1 on endothelial cells appears to be the molecular mechanism governing PMN endothelial cell interaction and subsequent endothelial cell damage resulted from GIR.