Simo I E, Yakichuk J A, Ooi T C
Metabolism Laboratory, Ottawa Civic Hospital, University of Ottawa, Ontario, Canada.
Atherosclerosis. 1993 Apr;100(1):55-64. doi: 10.1016/0021-9150(93)90067-5.
Eleven men with hypoalphalipoproteinemia (HPAL; fasting plasma high density lipoprotein (HDL) cholesterol level of < 0.9 mmol/l), mild hypertriglyceridemia (HTG; triglycerides (TG) level of 1.75-7.5 mmol/l) and a normal calculated LDL cholesterol level (< 3.7 mmol/l) participated in a randomized, double-blind, double-placebo, crossover trial to compare the effect of two drugs, lovastatin (40 mg once daily) and gemfibrozil (600 mg twice daily), on clearance of postprandial lipoproteins. A 2-week washout period separated drug treatment periods of 6 weeks each. Ten subjects completed each treatment period. After ingestion of a vitamin A fat load, plasma, chylomicron and non-chylomicron retinyl palmitate (RP) and TG responses (areas under curves) were reduced in all subjects on gemfibrozil therapy and in 7 on lovastatin therapy. There was close correlation between change in fasting TG (but not fasting HDL-cholesterol) and change in postprandial RP areas on gemfibrozil but not lovastatin therapy. Postheparin lipoprotein lipase (LPL) and hepatic lipase (HL) activities were increased by gemfibrozil therapy while only a mild elevation in LPL activity alone was seen on lovastatin therapy. These data indicate that improvement in HTG is the main feature associated with improvement in postprandial lipemia and this is likely due to LPL-mediated enhancement of lipolytic hydrolysis. Gemfibrozil is more effective than lovastatin in attenuating postprandial lipemia in the HPAL/HTG syndrome.
11名患有低α脂蛋白血症（HPAL；空腹血浆高密度脂蛋白（HDL）胆固醇水平<0.9 mmol/l）、轻度高甘油三酯血症（HTG；甘油三酯（TG）水平为1.75 - 7.5 mmol/l）且计算得出的低密度脂蛋白胆固醇水平正常（<3.7 mmol/l）的男性参与了一项随机、双盲、双安慰剂、交叉试验，以比较两种药物洛伐他汀（每日一次，40 mg）和吉非贝齐（每日两次，600 mg）对餐后脂蛋白清除的影响。两个为期6周的药物治疗期之间有2周的洗脱期。每个治疗期有10名受试者完成。在摄入维生素A脂肪负荷后，接受吉非贝齐治疗的所有受试者以及接受洛伐他汀治疗的7名受试者的血浆、乳糜微粒和非乳糜微粒视黄醇棕榈酸酯（RP）及TG反应（曲线下面积）均降低。在吉非贝齐治疗中，空腹TG（而非空腹HDL胆固醇）的变化与餐后RP面积的变化密切相关，但在洛伐他汀治疗中并非如此。吉非贝齐治疗可增加肝素后脂蛋白脂肪酶（LPL）和肝脂肪酶（HL）活性，而洛伐他汀治疗仅使LPL活性有轻度升高。这些数据表明，HTG的改善是与餐后血脂异常改善相关的主要特征，这可能是由于LPL介导的脂解水解增强所致。在HPAL/HTG综合征中，吉非贝齐在减轻餐后血脂异常方面比洛伐他汀更有效。
