Gaw A, Packard C J, Lindsay G M, Murray E F, Griffin B A, Caslake M J, Colquhoun I, Wheatley D J, Lorimer A R, Shepherd J
Institute of Biochemistry, Glasgow Royal Infirmary, UK.
Arterioscler Thromb Vasc Biol. 1996 Feb;16(2):236-49. doi: 10.1161/01.atv.16.2.236.
The effects of colestipol therapy alone (20 g/d) or combined with simvastatin (20 mg/d) were examined in a group of eight male patients with primary moderate hypercholesterolemia (total cholesterol > or = 6.5 mmol/L [> or = 250 mg/dL]) who had undergone coronary artery bypass grafting more than 3 months previously. Colestipol therapy decreased total cholesterol by 14% (P < .001) and LDL cholesterol (LDL-C) by 23% (P < .001), while dual therapy decreased total cholesterol by 38% and LDL-C by 52% (both P < .001 versus baseline). No significant changes were observed in plasma triglyceride, VLDL cholesterol, or HDL cholesterol levels. VLDL subfraction turnovers were conducted at baseline and again on each regimen. ApoB kinetic parameters derived from a multicompartmental model suggested that colestipol therapy resulted in an expansion of the total VLDL apoB pool (36%, P < .05) that was largely due to a fall in the clearance rate of VLDL1 apoB (49%), while the LDL apoB pool decreased 23% as a result of diminished direct LDL input. The model used also revealed that addition of simvastatin to the resin therapy caused increases in the fractional transfer rates of VLDL2 to IDL and IDL to LDL together with a 37% increment in the LDL apoB fractional catabolic rate. Compared with baseline, combined therapy generated falls in both IDL (35%, P = .01) and LDL (37%, P < .04) apoB pools due to enhanced clearance of IDL (214%, P < .03) and reduced total input of LDL (39%, P < .003).
在一组8名男性原发性中度高胆固醇血症患者（总胆固醇≥6.5 mmol/L[≥250 mg/dL]）中，研究了单独使用考来替泊治疗（20 g/天）或与辛伐他汀联合使用（20 mg/天）的效果，这些患者在3个多月前接受了冠状动脉搭桥手术。考来替泊治疗使总胆固醇降低了14%（P<.001），低密度脂蛋白胆固醇（LDL-C）降低了23%（P<.001），而联合治疗使总胆固醇降低了38%，LDL-C降低了52%（与基线相比，P均<.001）。血浆甘油三酯、极低密度脂蛋白胆固醇或高密度脂蛋白胆固醇水平未观察到显著变化。在基线时以及每种治疗方案下再次进行极低密度脂蛋白亚组分周转率测定。从多室模型得出的载脂蛋白B动力学参数表明，考来替泊治疗导致总极低密度脂蛋白载脂蛋白B池扩大（36%，P<.05），这主要是由于极低密度脂蛋白1载脂蛋白B清除率下降（49%），而低密度脂蛋白载脂蛋白B池因直接低密度脂蛋白输入减少而下降23%。所使用的模型还显示，在树脂治疗中添加辛伐他汀会导致极低密度脂蛋白2向中间密度脂蛋白以及中间密度脂蛋白向低密度脂蛋白的分数转运率增加，同时低密度脂蛋白载脂蛋白B分数分解代谢率增加37%。与基线相比，联合治疗使中间密度脂蛋白（35%，P=.01）和低密度脂蛋白（37%，P<.04）载脂蛋白B池均下降，这是由于中间密度脂蛋白清除率提高（214%，P<.03）和低密度脂蛋白总输入减少（39%，P<.003）。
