Lansink Maren Oude, Görlinger Klaus, Hartmann Matthias, de Groot Herbert, Effenberger-Neidnicht Katharina
Institute for Physiological Chemistry, University Hospital Essen, Essen, Germany.
Department of Anaesthesiology and Intensive Care, University Hospital Essen, Essen, Germany; TEM International GmbH, Munich, Germany.
Thromb Res. 2016 Mar;139:38-43. doi: 10.1016/j.thromres.2015.10.025. Epub 2015 Oct 28.
Inhibitory effects of exogenous melatonin (MLT) on plasma coagulation and platelet aggregation have already been observed in vivo and in vitro under normal conditions. Here, we studied whether MLT also diminishes the lipopolysaccharide (LPS)-induced disseminated intravascular coagulation (DIC) during subacute endotoxaemia.
Subacute endotoxaemia was induced in male Wistar rats by an intravenous infusion of LPS over a period of 300min (0.5mg LPS/kg×h). MLT was administered intravenously 15min before and 120min and 240min after starting of the LPS infusion (3×3mg MLT/kg×15min). The kinetic of clot formation was analysed by thromboelastometry.
Infusion of LPS led initially to a significant reduction of clotting time (120min, LPS: 150±21s vs. SHAM: 292±36s), and finally a significant increase of clotting time (300min, LPS: 2768±853s vs. SHAM: 299±67s) and a slight increase of clot formation time (300min, LPS: 1038±657s vs. SHAM: 98±14s) as well as a significant decrease of alpha-angle (300min, LPS: 35±15° vs. SHAM: 72±3°), maximum clot firmness (300min, LPS: 22±6mm vs. SHAM: 68±3mm), and area under the curve (300min, LPS: 1657±552mm×100 vs. SHAM: 6849±307mm×100). Simultaneously, a decrease of platelet count (300min, LPS: 55±8 vs. SHAM: 180±55) and a release of cell-free haemoglobin (240min, LPS: 46±5μmol/L vs. SHAM: 16±2μmol/L) could be observed in the course of subacute endotoxaemia. The additional administration of MLT did not reduce the LPS-induced alterations in parameters of thromboelastometry, but significantly reduced the LPS-induced decrease of platelet count (300min, LPS+MLT: 130±10) and release of cell-free haemoglobin (240min, LPS+MLT: 29±3μmol/L).
Melatonin does not affect DIC but diminishes thrombocytopenia and haemolysis during endotoxaemia.
在正常条件下，已在体内和体外观察到外源性褪黑素（MLT）对血浆凝血和血小板聚集的抑制作用。在此，我们研究了MLT是否也能减轻亚急性内毒素血症期间脂多糖（LPS）诱导的弥散性血管内凝血（DIC）。
通过在300分钟内静脉输注LPS（0.5mg LPS/kg×h）诱导雄性Wistar大鼠发生亚急性内毒素血症。在开始输注LPS前15分钟以及输注LPS后120分钟和240分钟静脉注射MLT（3×3mg MLT/kg×15分钟）。通过血栓弹力图分析凝血形成动力学。
输注LPS最初导致凝血时间显著缩短（120分钟，LPS组：150±21秒 vs. 假手术组：292±36秒），最终凝血时间显著延长（300分钟，LPS组：2768±853秒 vs. 假手术组：299±67秒），凝血形成时间略有增加（300分钟，LPS组：1038±657秒 vs. 假手术组：98±14秒），同时α角显著减小（300分钟，LPS组：35±15° vs. 假手术组：72±3°）、最大血凝块硬度显著降低（300分钟，LPS组：22±6毫米 vs. 假手术组：68±3毫米）以及曲线下面积显著减小（300分钟，LPS组：1657±552毫米×100 vs. 假手术组：6849±307毫米×100）。同时，在亚急性内毒素血症过程中可观察到血小板计数降低（300分钟，LPS组：55±8 vs. 假手术组：180±55）以及游离血红蛋白释放（240分钟，LPS组：46±5μmol/L vs. 假手术组：16±2μmol/L）。额外给予MLT并未减轻LPS诱导的血栓弹力图参数改变，但显著减轻了LPS诱导的血小板计数降低（300分钟，LPS + MLT组：130±10）和游离血红蛋白释放（240分钟，LPS + MLT组：29±3μmol/L）。
褪黑素不影响DIC，但可减轻内毒素血症期间的血小板减少和溶血。
