The effect of intestinal ischemia and reperfusion injury on ICAM-1 expression, endothelial barrier function, neutrophil tissue influx, and protease inhibitor levels in rats
The effect of intestinal ischemia and reperfusion injury on ICAM-1 expression, endothelial barrier function, neutrophil tissue influx, and protease inhibitor levels in rats
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DOI：
10.1097/00024382-200207000-00016
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发表时间：
2002-07-01
期刊：
影响因子：
3.1
通讯作者：
Andersson, R
中科院分区：
文献类型：
--
作者：
Olanders, K;Sun, ZW;Andersson, R
多器官功能障碍综合征（MODS）是由复杂的机制介导的，其中活化的白细胞和内皮细胞之间的相互作用起着核心作用。ICAM-1（细胞间粘附分子-1）介导活化的白细胞从毛细血管后小静脉到组织的牢固粘附和跨内皮迁移。本研究采用双单克隆抗体技术（n = 36）测定大鼠肠缺血40 min和再灌注1、3、6、12 h后各脏器中ICAM-1的表达。利用放射性标记的人血清白蛋白血管渗漏也评估了内皮屏障的通透性（n = 12）。用髓过氧化物酶活性测定肺中中性粒细胞的隔离，用电免疫法测定血浆蛋白酶抑制剂的水平。ICAM-1的表达在各器官间存在显著的区域差异，无论是构成性损伤还是I/ r损伤后。在肝脏和肺部观察到最高的组成水平，其次是肾脏。肠和心脏的组成型ICAM-1表达量约为肝脏和肺部的1/20。大脑和肌肉的水平大约是肝脏和肺部的1/150。肠I/R后，肺、肠、脑、心脏和肌肉的I/R显著增加（17-45%）。I/ r损伤后，各脏器白蛋白渗漏指数（ALI）和肺髓过氧化物酶活性均升高。I/R刺激后血清白蛋白和大多数蛋白酶抑制剂水平显著下降。肠道I/R导致全身ICAM-1表达增加，并伴有明显的器官变异性。ICAM-1的上调可能代表了活化白细胞粘附和迁移过程的关键步骤，并可能在组织损伤的发展中发挥作用。
Multiple organ dysfunction syndrome (MODS) is mediated by complex mechanisms in which interactions between activated leukocytes and endothelial cells play a central role. ICAM-1 (intercellular adhesion molecule-1) mediates firm adhesion and transendothelial migration of activated leukocytes from postcapillary venules into the tissue. The present study evaluated the ICAM-1 expression in various organs after 40 min of intestinal ischemia and 1, 3, 6, 12 h of reperfusion (I/R) in the rat, using a dual monoclonal antibody technique (n = 36). Endothelial barrier permeability, using the vascular leakage of radiolabeled human serum albumin was also assessed (n = 12). Neutrophil sequestration in the lungs was quantitated by myeloperoxidase activity and plasma protease inhibitor levels were measured with electroimmunoassay. Significant regional differences were found in ICAM-1 expression between organs, both constitutively and after I/R-injury. The highest constitutive levels were observed in the liver and lungs, followed by the kidneys. The constitutive ICAM-1 expression in the intestines and in the heart was about 1/20 compared with that found in the liver and lungs. The brain and muscle had levels of about 1/150 of that in the liver and lungs. After intestinal I/R, significant increases (17-45%) were found in the lungs, intestines, brain, heart, and muscle. Albumin leakage index (ALI) in all examined organs and myeloperoxidase activity in the lungs increased after I/R-injury. Serum levels of albumin and most protease inhibitors decreased significantly after I/R challenge. Intestinal I/R results in an increase of systemic ICAM-1 expression with marked organ variability. The upregulation of ICAM-1 could represent a crucial step in the adherence- and migration process of activated leukocytes and potentially in the development of tissue injury.