Okumura Y, Inoue H, Fujiyama Y, Bamba T
Second Department of Internal Medicine, Shiga University of Medical Science, Otsu, Japan.
J Gastroenterol. 1995 Jun;30(3):379-86. doi: 10.1007/BF02347515.
The administration of a high-dose of a serine protease inhibitor is recommended in patients complicated by multiple organ failure (MOF), including adult respiratory distress syndrome (ARDS), induced by acute pancreatitis. The accumulation of polymorphonuclear leukocytes (PMN) in affected organs is considered to be one of the causative factors of MOF. Adhesion to endothelial cells (EC), via adhesion molecules, and the transendothelial migration of PMN is closely associated with the accumulation of PMN. We examined the effects of two serine protease inhibitors, ulinastatin (UT) and gabexate mesilate (GM), on EC-PMN adhesion and transendothelial migration in human umbilical vein EC and 51Cr-labeled PMN in vitro. EC-PMN adhesion, and the expression of intercellular adhesion molecule-1 (ICAM-1) and endothelial cell adhesion molecule-1 (ELAM-1) on EC induced by IL-1 beta and TNF alpha, were reduced by the pretreatment of EC with these inhibitors. The transendothelial migration of PMN stimulated by IL-8 was also inhibited by pretreating PMN with UT or GM. We also examined whether these inhibitors reduced PMN accumulation in the lung in rats with acute pancreatitis induced by a closed duodenal loop. The myeloperoxidase activity in and histological findings of the lung suggested that UT and GM reduced PMN accumulation. In conclusion, serine protease inhibitors may inhibit PMN accumulation in ARDS due to acute pancreatitis.
对于因急性胰腺炎并发多器官功能衰竭（MOF），包括成人呼吸窘迫综合征（ARDS）的患者，建议给予高剂量的丝氨酸蛋白酶抑制剂。多形核白细胞（PMN）在受影响器官中的积聚被认为是MOF的致病因素之一。PMN通过黏附分子与内皮细胞（EC）黏附以及跨内皮迁移与PMN的积聚密切相关。我们在体外研究了两种丝氨酸蛋白酶抑制剂，乌司他丁（UT）和甲磺酸加贝酯（GM）对人脐静脉内皮细胞（EC）与51Cr标记的PMN之间的内皮细胞-多形核白细胞黏附及跨内皮迁移的影响。用这些抑制剂预处理内皮细胞可减少IL-1β和TNFα诱导的内皮细胞-多形核白细胞黏附以及细胞间黏附分子-1（ICAM-1）和内皮细胞黏附分子-1（ELAM-1）在EC上的表达。用UT或GM预处理PMN也可抑制IL-8刺激的PMN跨内皮迁移。我们还研究了这些抑制剂是否能减少由闭合十二指肠环诱导的急性胰腺炎大鼠肺内的PMN积聚。肺组织中的髓过氧化物酶活性和组织学结果表明，UT和GM可减少PMN积聚。总之，丝氨酸蛋白酶抑制剂可能抑制急性胰腺炎所致ARDS中的PMN积聚。
