Chen M F, Wang T D, Yeh H T, Hsu H C, Lee Y T
Department of Internal Medicine (Cardiology), National Taiwan University Medical Center, Taipei, Taiwan.
Eur J Clin Invest. 2001 Aug;31(8):707-13. doi: 10.1046/j.1365-2362.2001.00868.x.
Studies suggest that both oxidized low and high density lipoprotein (LDL and HDL) play a role in the pathogenesis of atherosclerosis. Gemfibrozil is widely used and is reported to increase cholesterol of LDL and HDL in hypertriglyceridemic patients. The aim of this study was to investigate the effect of gemfibrozil treatment on the oxidative status of lipoprotein particles in Fredrickson phenotype IV hypertriglyceridemic patients.
Twenty-two patients, aged 38-64 years, with fasting plasma triglyceride concentrations between 2.90 and 8.97 mmol L(-1), were recruited and were given gemfibrozil 300 mg three times daily for 12 weeks. Venous blood samples were collected before gemfibrozil treatment, after 4, 8, or 12 weeks of treatment, and 4 weeks after termination of treatment, and used to analyse the plasma lipid profile, isolate lipoproteins, and analyse the chemical composition and in vitro oxidation of lipoprotein particles.
Gemfibrozil treatment resulted in a decrease in plasma total triglyceride levels and the triglyceride content of all lipoproteins. Plasma total cholesterol levels were decreased as a result of a decrease in very low density lipoprotein (VLDL) cholesterol levels. A slight increase in LDL cholesterol levels was observed, whereas the thiobarbituric acid-reactive substances (TBARS) of LDL were decreased and the lag and peak time of LDL to oxidation were unchanged and maximal diene production was decreased. Plasma HDL cholesterol levels, the surface-to-core ratio of HDL particles, and the resistance of HDL to oxidation were increased.
The decreased TBARS and diene production of LDL, increased HDL cholesterol levels, and increased resistance of HDL to oxidation may, in part, explain why gemfibrozil treatment was found to be generally beneficial in terms of protection against coronary heart disease.
研究表明,氧化型低密度脂蛋白(LDL)和高密度脂蛋白(HDL)在动脉粥样硬化的发病机制中均起作用。吉非贝齐被广泛使用,据报道,它可使高甘油三酯血症患者的LDL和HDL胆固醇升高。本研究的目的是探讨吉非贝齐治疗对弗雷德里克森IV型高甘油三酯血症患者脂蛋白颗粒氧化状态的影响。
招募了22名年龄在38 - 64岁之间、空腹血浆甘油三酯浓度在2.90至8.97 mmol/L之间的患者,给予吉非贝齐300 mg,每日三次,共12周。在吉非贝齐治疗前、治疗4周、8周或12周后以及治疗终止后4周采集静脉血样本,用于分析血浆脂质谱、分离脂蛋白,并分析脂蛋白颗粒的化学成分和体外氧化情况。
吉非贝齐治疗导致血浆总甘油三酯水平以及所有脂蛋白的甘油三酯含量降低。由于极低密度脂蛋白(VLDL)胆固醇水平降低,血浆总胆固醇水平下降。观察到LDL胆固醇水平略有升高,而LDL的硫代巴比妥酸反应性物质(TBARS)降低,LDL氧化的延迟时间和峰值时间未改变,最大二烯生成量减少。血浆HDL胆固醇水平、HDL颗粒的表面与核心比率以及HDL对氧化的抵抗力增加。
LDL的TBARS和二烯生成减少、HDL胆固醇水平升高以及HDL对氧化的抵抗力增加,可能部分解释了为什么发现吉非贝齐治疗在预防冠心病方面总体有益。