Richards Guy A, Theron Annette, Tintinger Gregory, Anderson Ronald
Department of Critical Care, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2193, South Africa.
Department of Immunology, Faculty of Health Sciences, University of Pretoria, Pretoria 0001, South Africa.
Pharmaceuticals (Basel). 2018 May 14;11(2):46. doi: 10.3390/ph11020046.
Dabigatran is an oral direct thrombin inhibitor, and rivaroxaban, a factor Xa inhibitor. Dabigatran has been implicated in the etiology of acute coronary syndromes and as these occur following inflammatory changes in the endothelium, we investigated the inflammatory potential of these agents in vitro. In order to do so, polymorphonuclear leukocytes (PMNL) were isolated from heparinized venous blood from non-smoking, healthy adults and exposed to dabigatran or rivaroxaban (0.5⁻10 µM). Generation of reactive oxygen species (ROS), elastase release, cytosolic Ca fluxes, neutrophil extracellular trap (NET) formation and cell viability were measured using chemiluminescence, spectrophotometric and flow cytometric procedures respectively. However, with the exception of modest inhibitory effects on elastase release, neither agent at concentrations of up to 10 µM affected these markers of PMNL activation. Although no pro-inflammatory effects of dabigatran nor any difference between the two test agents were detected in vitro, the existence of a pro-inflammatory mechanism involving the generation of thrombin during dabigatran therapy cannot be fully excluded.
达比加群是一种口服直接凝血酶抑制剂，利伐沙班是一种Xa因子抑制剂。达比加群与急性冠脉综合征的病因有关，由于这些综合征发生在内皮炎症改变之后，我们在体外研究了这些药物的炎症潜力。为此，从非吸烟健康成年人的肝素化静脉血中分离出多形核白细胞（PMNL），并将其暴露于达比加群或利伐沙班（0.5 - 10 μM）中。分别使用化学发光、分光光度和流式细胞术程序测量活性氧（ROS）的产生、弹性蛋白酶释放、胞质钙通量、中性粒细胞胞外陷阱（NET）形成及细胞活力。然而，除了对弹性蛋白酶释放有适度抑制作用外，浓度高达10 μM的两种药物均未影响这些PMNL活化标志物。虽然在体外未检测到达比加群的促炎作用，也未发现两种受试药物之间存在差异，但不能完全排除达比加群治疗期间存在涉及凝血酶生成的促炎机制。
