脂蛋白的氧化修饰对血凝及纤溶活性的影响

Effects of oxidative modification of lipoproteins on blood coagulation and fibrinolysis

目的 :研究脂蛋白的氧化修饰对凝血及纤溶活性的影响。方法 :用Cu2 + 法及次氯酸法氧化修饰超速离心分离的正常人血浆极低密度脂蛋白 (VLDL)、低密度脂蛋白 (LDL)及高密度脂蛋白 (HDL)。分别将天然及氧化修饰脂蛋白N -VLDL、Ox -VLDL ;N -LDL、Ox -LDL、N -HDL及Ox -HDL加入由正常人新鲜混合血浆构成的反应系统中 ,以相应天然脂蛋白为对照 ,测定凝血酶原时间 (PT)、活化部分凝血酶原时间 (APTT)、组织型纤溶酶原激活物(t-PA)活性、纤溶酶原激活物抑制剂 1(PAI - 1)活性及血小板最大聚集率。结果 :VLDL、LDL及HDL经Cu2 + 法及次氯酸法氧化修饰后其REM、2 34nm吸光度值、TBARS含量均显著大于对照组 (P <0 0 1)。Ox -VLDL、Ox -LDL及Ox -HDL使PT及APTT明显短于对照组 (P <0 0 5或P <0 0 1) ,血小板聚集率明显高于对照组 (P <0 0 1)。Ox -VLDL及Ox -LDL使t-PA活性高于对照组 ,PAI- 1活性低于对照组 (P <0 0 5及P <0 0 1) ,而Ox -HDL对t-PA活性及PAI- 1活性的影响与对照组无明显差别。结论 :N -VLDL、N -LDL及N -HDL对凝血及纤溶活性无影响。Ox -VLDL、Ox -LDL及Ox -HDL促进血凝及血栓形成 ;Ox -VLDL及Ox -LDL使纤溶活性增加 ,而Ox

AIM: To study the effects of oxidative modification lipoproteins on blood coagulation and fibrino (lysis) in vitro. METHODS: Normal human plasma VLDL, LDL and HDL, which were isolated by density gradient ultracentrifugation method, were oxidatively modified by Cu^(2+) and HOCl method. N-VLDL, Ox-VLDL, N-LDL, Ox-LDL, N-HDL, Ox-HDL were added to the reaction system which consisted of mixed fresh normal plasma respectively, prothrombin time (PT), activated partial thrombplastin time (APTT), plasminogen activator inhibitor 1 (PAI-1), tissue plasminogen activator (t-PA) and platelet aggregation were measured according to the direction of the kits. RESULTS: The relative electrophoretic mobility (REM), absorbance at 234nm and TBARS of oxidized VLDL, LDL and HDL mediated by HOCl or Cu^(2+) were significantly higher than that of the control group (P<0.01). N-VLDL, (N-LDL) and N-HDL had no effect on PT, APTT, t-PA, PAI-1 and platelet aggregation. The PT and APTT of (Ox-VLDL,) Ox-LDL and Ox-HDL were significantly shorter than that of the control group (P<0.05 and (P<0.01)). The platelet aggregation of Ox-VLDL, Ox-LDL and Ox-HDL were significantly stronger than that of the control group (P<0.01). The Ox-VLDL and Ox-LDL were higher in t-PA and lower in PAI-1 than that of the control group (P<0.05 and (P<0.01)), but the Ox-HDL had no influences on t-PA and PAI-1 activity. CONCLUSIONS: N-VLDL, N-LDL and N-HDL have no effects on blood coagulation and fibrinolysis in vitro. Ox-VLDL, Ox-LDL and Ox-HDL enhance blood coagulation and thrombosis. Ox-VLDL and Ox-LDL enhance t-PA activity and decreased PAI-1 activity, but Ox-HDL does not affect the fibrinolysis activity. [