Lagrost L, Athias A, Lemort N, Richard J L, Desrumaux C, Châtenet-Duchêne L, Courtois M, Farnier M, Jacotot B, Braschi S, Gambert P
Laboratoire de Biochimie des Lipoprotéines, INSERM U498, Faculté de Médecine, Hôpital du Bocage, Dijon, France.
Atherosclerosis. 1999 Apr;143(2):415-25. doi: 10.1016/s0021-9150(98)00299-8.
The aim of the present study was to search in type IIb hyperlipidemic patients for putative concomitant effects of simvastatin on the physicochemical characteristics of low density lipoproteins (LDL) and high density lipoproteins (HDL), as well as on the activities of the cholesteryl ester transfer protein (CETP) and the phospholipid transfer protein (PLTP) that were determined in both endogenous lipoprotein-dependent and endogenous lipoprotein-independent assays. In a double-blind, randomized trial, patients received either placebo (one tablet/day; n = 12) or simvastatin (20 mg/day; n = 12) for a period of 8 weeks after a 5-week run-in period. Simvastatin, unlike placebo, reduced the lipid and apolipoprotein B contents of the most abundant LDL-1, LDL-2, and LDL-3 subfractions without inducing significant changes in the overall size distribution of LDL and HDL. Whereas simvastatin significantly increased PLTP activity in an endogenous lipoprotein-dependent assay (P < 0.01), no variation was observed in a lipoprotein-independent assay. Simvastatin significantly decreased plasma CETP activity in an endogenous lipoprotein-dependent assay (P < 0.01), and the reduction in plasma cholesteryl ester transfer rates was explained by a 16% drop in CETP mass concentration (P < 0.01). In contrast, the specific activity of CETP was unaffected by the simvastatin treatment reflecting at least in part the lack of significant alteration in plasma triglyceride-rich lipoprotein acceptors. The simvastatin-induced changes in plasma CETP mass levels correlated positively with changes in plasma CETP activity (r = 0.483, P = 0.0561), in total cholesterol levels (r = 0.769; P < 0.01), and in LDL-cholesterol levels (r = 0.736; P < 0.01). Whereas the observations suggest that simvastatin might exert concomitant beneficial effects on plasma CETP and LDL levels, neither plasma cholesteryl ester transfer activity nor plasma phospholipid transfer activity appeared as the main determinants of the LDL and HDL distribution profiles in type IIb hyperlipidemic patients.
本研究的目的是在IIb型高脂血症患者中探究辛伐他汀对低密度脂蛋白（LDL）和高密度脂蛋白（HDL）理化特性的潜在伴随效应，以及对胆固醇酯转运蛋白（CETP）和磷脂转运蛋白（PLTP）活性的影响，这些活性是在内源性脂蛋白依赖性和内源性脂蛋白非依赖性试验中测定的。在一项双盲、随机试验中，患者在为期5周的导入期后，接受安慰剂（每日1片；n = 12）或辛伐他汀（每日20 mg；n = 12）治疗8周。与安慰剂不同，辛伐他汀降低了最丰富的LDL-1、LDL-2和LDL-3亚组分的脂质和载脂蛋白B含量，而未引起LDL和HDL总体大小分布的显著变化。在一项内源性脂蛋白依赖性试验中，辛伐他汀显著增加了PLTP活性（P < 0.01），而在一项脂蛋白非依赖性试验中未观察到变化。在一项内源性脂蛋白依赖性试验中，辛伐他汀显著降低了血浆CETP活性（P < 0.01），血浆胆固醇酯转运率的降低是由于CETP质量浓度下降16%所致（P < 0.01）。相反，CETP的比活性不受辛伐他汀治疗的影响，这至少部分反映了富含甘油三酯的血浆脂蛋白受体没有显著改变。辛伐他汀引起的血浆CETP质量水平变化与血浆CETP活性变化（r = 0.483，P = 0.0561）、总胆固醇水平变化（r = 0.769；P < 0.01）以及LDL胆固醇水平变化（r = 0.736；P < 0.01）呈正相关。尽管这些观察结果表明辛伐他汀可能对血浆CETP和LDL水平产生伴随的有益影响，但在IIb型高脂血症患者中，血浆胆固醇酯转运活性和血浆磷脂转运活性似乎都不是LDL和HDL分布模式的主要决定因素。
