Yang C Y, Gu Z W, Xie Y H, Valentinova N V, Yang M, Yeshurun D, Quion J A, Gotto A M
Department of Medicine, Baylor College of Medicine, Houston TX, USA.
Atherosclerosis. 1996 Sep 27;126(1):105-16. doi: 10.1016/0021-9150(96)05899-6.
To examine the effects of gemfibrozil on very-low-density lipoprotein (VLDL) composition and low-density lipoprotein (LDL) size, five men with hypertriglyceridemia (HTG) alone and five men with HTG and hypercholesterolemia (combined hyperlipidemia, CHLP) were randomized for 8 weeks to Lopid SR (slow-release gemfibrozil; two 600-mg tablets once per day) or placebo in a crossover study. Drug therapy versus placebo significantly decreased plasma triglyceride (68%), and VLDL (77%), and significantly increased high-density lipoprotein cholesterol (25%); total cholesterol, apolipoprotein B and lipoprotein[a] concentrations did not change significantly. With drug, mean total apoE in plasma was 53% lower in patients with HTG and 39% lower in patients with CHLP. Gemfibrozil significantly affected VLDL composition: protein increased 26%, molar ratio of apoE to apoB reduced 48%, apoC-II increased 19%, and apoC-III decreased 9%. LDL cholesteryl ester significantly increased with drug treatment. VLDL subfractions were separated and classified as heparin binding (VLDLR, apoE rich) or nonbinding (VLDLNR-1 and VLDLNR-2, both apoE poor). All VLDL subfractions were significantly lower with drug therapy, and the differences for total VLDL and for VLDL subfractions were greater in patients with HTG. With placebo, VLDLR accounted for 41.8% of VLDL in HTG and 49.0% of VLDL in CHLP, reduced to 27.6% and 38.6%, respectively, with gemfibrozil. Taken together, these results suggest that treatment with gemfibrozil reduces plasma concentrations of VLDL and alters the apoprotein composition of VLDL in a manner that may favor LDL- and VLDL-receptor-mediated clearance of the apoE-rich VLDL subfraction, thereby reducing TG-rich particle concentrations, and possibly reducing risk for coronary heart disease.
为研究吉非贝齐对极低密度脂蛋白（VLDL）组成及低密度脂蛋白（LDL）大小的影响，在一项交叉研究中，将5名单纯高甘油三酯血症（HTG）男性和5名高甘油三酯血症合并高胆固醇血症（混合性高脂血症，CHLP）男性随机分组，接受为期8周的乐必妥缓释片（缓释吉非贝齐；每日2次，每次2片600毫克）或安慰剂治疗。与安慰剂相比，药物治疗显著降低了血浆甘油三酯（68%）和VLDL（77%），并显著升高了高密度脂蛋白胆固醇（25%）；总胆固醇、载脂蛋白B和脂蛋白[a]浓度无显著变化。用药后，HTG患者血浆中总载脂蛋白E平均降低53%，CHLP患者降低39%。吉非贝齐显著影响VLDL组成：蛋白质增加26%，载脂蛋白E与载脂蛋白B的摩尔比降低48%，载脂蛋白C-II增加19%，载脂蛋白C-III降低9%。药物治疗使LDL胆固醇酯显著增加。VLDL亚组分被分离并分为肝素结合型（VLDLR，富含载脂蛋白E）或非结合型（VLDLNR-1和VLDLNR-2，均缺乏载脂蛋白E）。药物治疗后所有VLDL亚组分均显著降低，且HTG患者中总VLDL及VLDL亚组分的差异更大。服用安慰剂时，VLDLR在HTG患者中占VLDL的41.8%，在CHLP患者中占49.0%，服用吉非贝齐后分别降至27.6%和38.6%。综上所述，这些结果表明，吉非贝齐治疗可降低血浆VLDL浓度，并改变VLDL的载脂蛋白组成，这可能有利于LDL和VLDL受体介导的富含载脂蛋白E的VLDL亚组分的清除，从而降低富含TG的颗粒浓度，并可能降低冠心病风险。
