Recombinant thrombomodulin improves the visceral microcirculation by attenuating the leukocyte-endothelial interaction in a rat LPS model
Recombinant thrombomodulin improves the visceral microcirculation by attenuating the leukocyte-endothelial interaction in a rat LPS model
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DOI：
10.1016/j.thromres.2012.11.025
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发表时间：
2013-04-01
影响因子：
7.5
通讯作者：
Yang, Daphne
中科院分区：
文献类型：
--
作者：
Iba, Toshiaki;Aihara, Koichiro;Yang, Daphne
前言：血管内皮功能异常在脓毒症器官功能障碍的发生发展中起重要作用。本研究旨在探讨重组血栓调节蛋白(RTM)对内毒素血症时白细胞-内皮细胞相互作用及随后的循环障碍的影响。材料与方法：Wistar大鼠于注射脂多糖(LPS)后2小时分别给予低、中、高剂量的RTM(n=7)。活体显微镜下观察治疗后肠系膜微循环变化。另一组(n=5)于注射脂多糖后5h测定血浆高迁移率族蛋白1(HMGB1)水平。结果：RTM治疗可抑制白细胞黏附、血栓形成和内皮损伤。然而，大剂量的RTM倾向于增加出血事件。因此，中剂量的RTM能更好地维持血流(P
Introduction: Abnormalities in vascular endothelial function play an important role in the development of septic organ dysfunction. The aim of this study was to examine the effect of recombinant thrombomodulin (rTM) on leukocyte-endothelial interaction and subsequent malcirculation in endotoxemia.Materials and Methods: Wistar rats were administered with either low, medium or high dose of rTM (n=7 each) 2 hours after lipopolysaccharide (LPS) infusion. Mesenteric microcirculation after the treatment was observed under the intravital microscopy. In another series (n=5 each), plasma levels of high-mobility group box 1 (HMGB1) levels were measured at 5 hours after LPS infusion.Results: Microscopic findings revealed suppression in leukocyte adhesion, thrombus formation and endothelial damage with the treatment by rTM. However, high-dose rTM tended to increase the bleeding events. Thus, blood flow was better maintained with medium-dose rTM (P