Gombás Judit, Kolev Krasimir, Tarján Eniko, Machovich Raymund
Department of Medical Biochemistry, Semmelweis University, Puskin u. 9., 1088 Budapest, Hungary.
Ann Hematol. 2004 Dec;83(12):759-63. doi: 10.1007/s00277-004-0928-x. Epub 2004 Aug 14.
The contribution of neutrophil leukocyte elastase (NE) to in vivo thrombolysis is still an open question. The present study examines the impact of variable levels of alpha1-proteinase inhibitor (alpha1-PI) (the major plasma inhibitor of NE) on fibrinolysis within the setting of thromboembolic diseases. Blood samples were taken from 56 patients with pulmonary thromboembolism prior to treatment. alpha1-PI and alpha1-PI-NE complex were measured in the serum and plasma with immunoturbidimetric and enzyme-linked immunosorbent assay (ELISA) methods, respectively. The fibrinolytic potential [spontaneous, tissue-type plasminogen activator (tPA) induced, and plasmin induced] of the plasma was evaluated in vitro with turbidimetric clot lysis assay. Correlation analysis (Pearson product-moment correlation coefficient, r) of the turbidimetric lysis parameters and the blood levels of alpha1-PI and alpha1-PI-NE complex was carried out. Fibrinolysis is slower in clots prepared from plasma containing elevated levels of alpha1-PI and alpha1-PI-NE complex. The maximal turbidity of the plasma clots shows significant correlation with the alpha1-PI level (r=0.39, p=0.003) and the correlation of the maximal turbidity and the tPA-induced lysis time is also significant (r=0.77, p<0.001). The lysis time correlates with the plasma level of alpha1-PI-NE complex, if fibrinolysis is induced with tPA (r=0.37, p=0.02), but not with plasmin (r=0.19, p=0.4). Our study shows that in pulmonary thromboembolism elevated levels of alpha1-PI are associated with suppressed plasma fibrinolytic potential. This effect can be at least partially explained by the coarse fibrin network structure and retarded plasminogen activator-dependent fibrinolysis.
中性粒细胞弹性蛋白酶（NE）对体内溶栓的作用仍是一个悬而未决的问题。本研究探讨了不同水平的α1-蛋白酶抑制剂（α1-PI）（NE的主要血浆抑制剂）对血栓栓塞性疾病纤溶作用的影响。在治疗前采集了56例肺血栓栓塞患者的血样。分别采用免疫比浊法和酶联免疫吸附测定（ELISA）法检测血清和血浆中的α1-PI及α1-PI-NE复合物。采用比浊法凝块溶解试验在体外评估血浆的纤溶潜力[自发、组织型纤溶酶原激活剂（tPA）诱导和纤溶酶诱导]。对比浊溶解参数与α1-PI和α1-PI-NE复合物血药浓度进行相关性分析（Pearson积矩相关系数，r）。由含有高水平α1-PI和α1-PI-NE复合物的血浆制备的凝块中纤溶作用较慢。血浆凝块的最大浊度与α1-PI水平呈显著相关（r = 0.39，p = 0.003），最大浊度与tPA诱导的溶解时间的相关性也很显著（r = 0.77，p < 0.001）。如果用tPA诱导纤溶，溶解时间与α1-PI-NE复合物的血浆水平相关（r = 0.37，p = 0.02），但与纤溶酶无关（r = 0.19，p = 0.4）。我们的研究表明，在肺血栓栓塞中，α1-PI水平升高与血浆纤溶潜力受抑制有关。这种效应至少可以部分由粗糙的纤维蛋白网络结构和纤溶酶原激活剂依赖性纤溶作用延迟来解释。
