纤维蛋白原、纤维蛋白及其降解产物对共培养血管内皮细胞纤溶活性的影响

目的研究纤维蛋白原（Fg）、纤维蛋白（Fb）及其降解产物（FDP）对共培养体系中人脐静脉内皮细胞组织型纤溶酶原激活物和纤溶酶原激活物抑制剂表达的影响。方法应用Transwell膜建立人脐静脉内皮细胞-兔主动脉平滑肌细胞共培养体系，在不同浓度（0、0．5、1．5、3．0、4．5和6．0g／L）Fg、Fb和FDP干预24h后，分别检测该共培养体系中人脐静脉内皮细胞组织型纤溶酶原激活物和纤溶酶原激活物抑制剂mRNA水平（RT-PCR法）以及培养上清中组织型纤溶酶原激活物和纤溶酶原激活物抑制剂抗原含量（ELISA法）与活性（发色底物法）的变化情况。结果Fg对组织型纤溶酶原激活物的表达没有显著影响，较高浓度的Fg（3．0～4．5g／L）可明显促进纤溶酶原激活物抑制剂mRNA表达、抗原含量及活性升高，但过高浓度的Fg（6．0g／L）却抑制纤溶酶原激活物抑制剂的表达。3．0-4．5g／L的Fb对组织型纤溶酶原激活物mRNA和抗原含量都起上调作用，同时显著下调组织型纤溶酶原激活物活性。较高浓度的Fb（1．5-4．5g／L）则可明显上调纤溶酶原激活物抑制剂的表达，且在mRNA、蛋白和活性水平趋势基本一致。3．0-6．0g／L的FDP均可明显下调组织型纤溶酶原激活物mRNA、蛋白和活性水平，1．5-6．0mg／ml的FDP均可促进纤溶酶原激活物抑制剂的高表达。结论Fg、Fb和FDP可以通过影响组织型纤溶酶原激活物和纤溶酶原激活物抑制剂的表达，引起纤溶活性降低，参与动脉粥样硬化的发展进程。

Effect of fibrinogen,fibrin and fibrin (ogen) degradation products on the tissue plasminogen activator and plasminogen activator inhibitor-1 expressions of vasculat endothelial cells in coculture system

Objective To investigate the effect of fibrinogen(Fg),fibrin(Fb)and fibrin(ogen) degradation products(FDPs)on tissue plasminogen activator(tPA)and plasminogen activator inhibitor-1 (PAI-1)expressions of human umbilical vein endothelial cells(HUVECs)in coculture system.Methods Fg,Fb and FDPs at various concentrations(0,0.5,1.5,3.0,4.5 and 6.0 g/L)were added to the transwell cocuhure system of HUVECs and smooth muscle cells (SMCs)for 24 hours.The expressions of tPA and PAI-1 at mRNA level were examined by RT-PCR and tPA and PAI-1 protein and activity were detected by ELISA and substrate chromogenic assays.Results tPA expression was not affected bv Fg.Fg at concentrations between 3.0-4.5 g/L significantly enhanced the mRNA expression,protein content and activity of PAI-1,while expression of PAI-1 was significantly inhibited by Fg at concentration of 6.0 g/L.Fb at concentrations between 3.0-4.5 g/L significantly up-regulated mRNA expression,increased protein content and downregulated activity of tPA.Fb(1.5-4.5 g/L)also enhanced the mRNA expression,increased protein content and activity of PAI-1.FDPs at concentrations 3.0-6.0 g/L down-regulated the expression of tPA and FDPs at concentrations 1.5-6.0 g/L significantly enhanced PAI-1 mRNA expression.Conclnsion Fg,Fb and FDPs play important roles in the pathogenesis of atherosclerosis by modulating the expression of tPA and PAI-1 of endothelial and SMCs.