内源性高甘油三酯血症患者血浆极低密度脂蛋白、低密度脂蛋白及高密度脂蛋白对血凝及纤维蛋白溶解的影响
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国家重点基础研究发展规划 973规划 (G2 0 0 0 0 5690 0 )资助


Effects of Plasma Very Low Density Lipoprotein,Low Density Lipoprotein and High Density Lipoprotein on Blood Coagulation and Fibrinolysis in Endogenous Hypertriglyceridemia
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    摘要:

    研究内源性高甘油三酯血症患者血浆极低密度脂蛋白、低密度脂蛋白及高密度脂蛋白是否发生了氧化修饰及其对凝血及纤维蛋白溶解活性的影响。对2 1例内源性高甘油三酯血症患者与2 1例年龄性别相近的正常人的血脂、脂质过氧化物进行了分析。用一次性密度梯度超速离心法分离血浆极低密度脂蛋白、低密度脂蛋白及高密度脂蛋白。测定这3种脂蛋白的2 34nm吸光度、相对电泳迁移率和硫代巴比妥酸反应物质含量。分别将这3种脂蛋白加入由正常人新鲜混合血浆构成的反应系统中,按试剂盒分别测定凝血酶原时间、活化部分凝血酶原时间、组织型纤溶酶原激活物活性及纤溶酶原激活物抑制剂1活性。内源性高甘油三酯血症患者血浆甘油三酯含量平均升高2 .73倍,高密度脂蛋白胆固醇下降1.71倍,同时硫代巴比妥酸反应物质含量升高1.2 2倍;内源性高甘油三酯血症组极低密度脂蛋白、低密度脂蛋白及高密度脂蛋白的2 34nm吸光度、相对电泳迁移率和硫代巴比妥酸反应物质含量均较对照组显著增加(P<0 .0 1) ,表明内源性高甘油三酯血症患者血浆极低密度脂蛋白、低密度脂蛋白及高密度脂蛋白均发生了氧化修饰,生成了氧化极低密度脂蛋白、氧化低密度脂蛋白及氧化高密度脂蛋白。凝血酶原时间及活化部分凝血酶原时间在分别加入内源性高甘油三酯血症组的极低密度脂蛋白、低密度脂蛋白及高密度脂蛋白后均比加入相应正常组脂蛋白明显缩短(P均<0 .0 5 )。内源性高甘油三酯血症组血浆极低密度脂蛋白使组织型纤维蛋白溶解酶原激活物活性升高,纤维蛋白溶解酶原激活物抑制剂1活性降低(P<0 .0 1) ,而内源性高甘油三酯血症组血浆低密度脂蛋白及高密度脂蛋白对组织型纤维蛋白溶解酶原激活物活性及纤维蛋白溶解酶原激活物抑制剂1活性无影响。相关分析表明,内源性高甘油三酯血症组血浆极低密度脂蛋白及高密度脂蛋白相对电泳迁移率与凝血酶原时间呈负相关(P<0 .0 1)。内源性高甘油三酯血症患者血浆极低密度脂蛋白、低密度脂蛋白及高密度脂蛋白发生了氧化修饰,并使凝血酶原时间及活化部分凝血酶原时间明显缩短,仅内源性高甘油三酯血症患者血浆极低密度脂蛋白增加纤维蛋白溶解活性,而内源性高甘油三酯血症患者血浆低密度脂蛋白及高密度脂蛋白对纤维蛋白溶解活性无影响

    Abstract:

    Aim To study whether plasma very low density lipoprotein (VLDL), low density Lipoprotein (LDL), high density lipoprotein (HDL) were oxidatively modified in endogenous hypertriglyceridemia and effects of VLDL, LDL and HDL on blood coagulation and fibrinolysis in vitro. Methods Plasma VLDL, LDL and HDL were isolated with density gradient ultracentrifugation method. Human plasma triglycerides (TG), total cholesterol (TC),high density lipoprotein cholesterol (HDLC) were measured by enzyme method. The oxidative modification of LDL, VLDL and HDL was identified by agarose gel relative electrophoretic mobility (REM), absorbance at 234 nm and fluorescence of thiobarbituric acid reaction substances (TBARS). Prothrombin time (PT),activated partial thrombplastin time (APTT), plasminogen activator inhibitor 1 (PAI 1) activity and tissue plasminogen activator (t PA) activity were measured in the reaction system consisted of freshly mixed normal plasma according to the direction of the kits. Results The hypertriglyceridemia (HTG) group were 1.6 and 0.4 times more plasma TG, TBARS level than the control group respectively (P<0.01). The plasma HDLC in HTG group was 32% lower than that of the control group (P<0.01). The rela tive electrophoretic mobility, absorbance at 234 nm and TBARS of VLDL, LDL and HDL in HTG group were significantly higher than that of the control group (P<0.01). The PT and APTT of VLDL, LDL and HDL in HTG group were significantly shorter than that of the control group (P<0.05). The t PA and VLDL in HTG group was higher and the PAI 1 in VLDL in HTG group was lower than that of the control group (P<0.01), but LDL and HDL were not influenced by the t PA and the PAI 1 in HTG group and the control group. The correlation analysis indicated that electrophoretic mobility of VLDL and HDL in HTG group was negatively correlated with PT (P<0.01). Conclusions Oxidative modification of plasma very low density lipoprotein, low density Lipoprotein, high density lipoprotein occurred in endogenous hypertriglyceridemia in vivo. LDL and HDL enhanced the activity of blood clotting system in vitro, but only VLDL affected the activity of fibrinolysis system.

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邓祖跃,刘秉文,刘宇,白怀,张祖辉.内源性高甘油三酯血症患者血浆极低密度脂蛋白、低密度脂蛋白及高密度脂蛋白对血凝及纤维蛋白溶解的影响[J].中国动脉硬化杂志,2003,11(2):93~98.

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  • 收稿日期:2002-12-04
  • 最后修改日期:2003-03-05
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