Kato H, Okada R, Oogushi K, Emura S, Kishikawa H, Kawazoye S, Fukuoka M, Takashima T, Ohmori K
Department of Internal Medicine, Saga Medical School, Nabeshima, Japan.
Angiology. 1998 Mar;49(3):211-20. doi: 10.1177/000331979804900307.
The aim of this study was to examine the suppressive effect of simvastatin on intramural coronary arterial lesions in cholesterol-fed rabbits. In one experiment, six groups of rabbits were fed laboratory chow alone or with added 0.1%, 0.2%, 0.3%, 0.5% or 1.0% cholesterol for 16 weeks. In another experiment, four groups of rabbits were fed a 0.5% cholesterol diet and treated with simvastatin at 1, 3, or 5 mg/kg/day or placebo. In each rabbit, the levels of serum total cholesterol (TC) were determined at 1-week intervals to calculate the integrated values. The lesion induction ratio was defined as the ratio of intramural coronary arteries 50-150 microm in diameter with arterial lipoidosis to the total number of arteries of the same diameter. In the two experiments, there were positive correlations between the lesion induction ratio and integrated TC (r=0.785, P<0.0001 and r=0.763, P<0.0001, respectively). The slopes of the regression lines for integrated TC obtained in the two experiments were similar, but the lesion induction ratio in the simvastatin-treated group was always lower, by about 14%, in comparison with that in the non-simvastatin-treated group. These findings suggest that simvastatin induces lesion reduction not only by reducing the levels of circulating cholesterol but also by directly suppressing the development of lipoidosis.
本研究的目的是检测辛伐他汀对喂食胆固醇的家兔壁内冠状动脉病变的抑制作用。在一项实验中，六组家兔分别单独喂食实验室饲料，或添加0.1%、0.2%、0.3%、0.5%或1.0%胆固醇，持续16周。在另一项实验中，四组家兔喂食0.5%胆固醇饮食，并分别以1、3或5mg/kg/天的剂量接受辛伐他汀治疗或给予安慰剂。每隔1周测定每只家兔的血清总胆固醇（TC）水平，以计算积分值。病变诱导率定义为直径50-150微米且伴有动脉脂质沉积的壁内冠状动脉数量与相同直径动脉总数的比值。在这两项实验中，病变诱导率与TC积分值之间均呈正相关（分别为r=0.785，P<0.0001和r=0.763，P<0.0001）。两项实验中获得的TC积分值回归线斜率相似，但与未接受辛伐他汀治疗的组相比，辛伐他汀治疗组的病变诱导率始终较低，约低14%。这些发现表明，辛伐他汀不仅通过降低循环胆固醇水平，还通过直接抑制脂质沉积的发展来减少病变。
