高脂血症患者低密度脂蛋白氧化易感性及调脂药物干预的影响

The oxidative susceptibility of low-density lipoprotein in hyperlipidemic patients and the effect of lipid-regulating drugs

目的 观察高脂血症对低密度脂蛋白 (LDL)氧化易感性的影响以及调脂药物干预后的改变。方法 应用短程密度梯度超速离心分离血浆LDL ,对 11例高甘油三酯血症患者口服微粒化非诺贝特 2 0 0mg d、10例高胆固醇血症患者口服普伐他汀 10mg d治疗 4周前、后和 6例正常人的LDL在体外以CuCl2 诱导氧化 ,测定LDL开始氧化的迟滞期和氧化速率。结果 (1)LDL氧化的迟滞期 :在高甘油三酯血症患者 [(43 8± 11 6 )min]和高胆固醇血症患者 [(40 8± 10 7)min]均较正常组 [(70 5±14 6 )min]明显缩短 (P均 <0 0 1)。 (2 )LDL的氧化速率 :在高甘油三酯血症患者 [(0 0 36± 0 0 0 4 )A min]和高胆固醇血症患者 [(0 0 31± 0 0 11)A min]均较正常组 [(0 0 2 0± 0 0 11)A min]明显增快 (P均 <0 0 5 )。 (3)高甘油三酯血症患者于微粒化非诺贝特治疗后LDL氧化的迟滞期 [(6 2 4± 5 0 )min]显著延长 (P <0 0 1) ,氧化速率 [(0 0 31± 0 0 0 3)A min]明显减慢 (P <0 0 5 )。 (4)高胆固醇血症患者于普伐他汀治疗后LDL氧化的迟滞期 [(5 8 8± 6 1)min]明显延长 (P <0 0 5 ) ,氧化速率 [(0 0 2 5± 0 0 0 9)A min]无显著性变化 (P >0 0 5 )。结论 高甘油三酯血症患者和高胆固醇血症患者LDL氧化易感性增?

Objective The purpose of this study is to investigate the effects of hypertriglyceridemia and hypercholesterolemia on the oxidative susceptibility of low density lipoprotein(LDL) Furthermore, the effects of micronised fenofibrate and pravastatin on LDL oxidative susceptibility in hypertriglyceridemic and hypercholesterolemic patients were also determined Methods LDL was separated by a short run density gradient ultracentrifugation from the plasma of 11 hypertriglyceridemic patients before and after the treatment with micronised fenofibrate at a dose of 200mg once daily for 4 weeks, 10 hypercholesterolemic patients before and after pravastatin therapy at a dose of 10mg once daily for 4 weeks and 6 healthy subjects as controls CuCl 2 induced oxidation of LDL was used to measure the rate of LDL oxidation and the lag time required for the initiation of CuCl 2 induced LDL oxidation Results (1) In terms of LDL oxidative kinetics, lag time in the hypertriglyceridemic group [(43 8±11 6)minutes] and hypercholesterolemic group [(40 8±10 7)minutes] were both shortened significantly compared with that in the controls [(70 5±14 6)minutes] (both P <0 01) The rate of LDL oxidation in the hypertriglyceridemic group [(0 036±0 004) A /min] and hypercholesterolemic group [(0 031±0 011) A /min] were much increased compared with that in the controls [(0 020±0 011) A /min] (both P <0 05) (2) In patients with hypertriglyceridemia, the lag time [(62 4±5 0)minutes] was much prolonged( P <0 01)and the rate of LDL oxidation [(0 031±0 003) A /min] decreased significantly ( P <0 05) after the treatment with micronised fenofibrate (3) In patients with hypercholesterolemia, the lag time [(58 8±6 1)minutes] was significantly prolonged( P <0 05), however, the rate of LDL oxidation [(0 025±0 009) A /min] was not reduced significantly after pravastatin therapy Conclusions (1) LDL are more susceptible to oxidative modifications both in hypertriglyceridemic and in hypercholesterolemic patients (2) The treatment with micronised fenofibrate could attenuate oxidative susceptibility of LDL in patients with hypertriglyceridemia (3) Pravastatin therapy may attenuate oxidative susceptibility of LDL in patients with hypercholesterolemia (4) The increased oxidative susceptibility of LDL may contribute to the atherogenic actions of hypertriglyceridemia and hypercholesterolemia (5) Improving endothelial function and increasing resistance of LDL oxidation may also be the mechanism for the beneficial effects of micronised fenofibrate or pravastatin and should now be regarded as a goal of therapy in the treatment of coronary heart disease