登革病毒诱导血管内皮细胞凝血和纤溶系统相关分子变化

目的为研究登革病毒感染血管内皮细胞所引起的凝血和纤溶分子表达变化.方法应用D2V感染生长良好的第2、3代脐静脉内皮细胞以观察内皮细胞在表达组织纤溶酶原激活物(tPA)、纤溶酶原激活物抑制物1(PAI-1)、凝血酶调节蛋白(TM)等分子变化.结果D2V可以显著上调内皮细胞的t-PA的表达并显著提高血浆可溶性凝血酶调节蛋白(sTM)和IL-6水平,而不影响PAI-1.抗IL-6抗体抑制D2V感染对内皮细胞表达t-PA和sTM的增强效应.结论血管内皮细胞是D2V的靶细胞之一,D2V可以诱导内皮细胞表达t-PA和IL-6并提高血浆中sTM水平,IL-6能有效地增强D2V诱导的纤溶和抗凝分子表达,高水平的t-PA和sTM可诱导纤溶亢进和抗凝效应增强,在IL-6诱导血管内皮细胞渗透性升高的前提下,有助于DHF/DSS患者出现血浆渗漏、血容量丢失甚至出血.

Dengue 2 virus induces molecular alteration in the coagulant and fibrinolytic pathways of human umbilical vein endothelial cells

Objective To study the changes of tissue plasminogen activator (t-PA), plasminogen activator inhibitor 1 (PAI-1), and soluble thrombomodulin (sTM) induced by dengue 2 virus (D 2V) infection of vascular endothelial cells. Methods The effects of D 2V infection on the production of t-PA, PAI-1, and sTM of human umbilical cord vein cells were studied. Results D 2V infection significantly induced the secretion of sTM and t-PA but showed no such effects on PAI-1 of human endothelial cells. Antibody against IL-6 inhibited D 2V-induced t-PA production of endothelial cells. A close correlation between serum levels of IL-6 and t-PA was found in dengue hemorrhagic fever (DHF) but not in dengue fever (DF) patients. Conclusion IL-6 can regulate D 2V-induced t-PA production of endothelial cells, suggesting that endothelial cells can be the target for D 2V infection and that D 2V-induced t-PA, TM, and IL-6 production of endothelial cells may contribute to the pathogenic development of dengue haemorrhagic fever/dengue shock syndrome (DHF/DSS).