烟酸缓释胶囊(锐旨)升高家兔高密度脂蛋白实验研究

Effect of Modified Release Capsule of Nicotinic Acid on Raising High Density Lipoprotein in Rabbits:Experimental Study

目的:观察烟酸缓释胶囊(锐旨)升高家兔高密度脂蛋白胆固醇(HDL-C)及其对动脉粥样硬化斑块的影响。方法:健康日本大耳白兔26只实验前适应性饲养2周,稳定后随即分组法分为:空白对照组8只,高脂模型组18只。其中空白对照组用普通兔饲料喂养22周;高脂模型组用高脂饲料(每kg普通兔饲料加1%胆固醇+8%熟猪油)喂养。10周后从高脂模型组中随即抽取2只处死。观察动脉斑块形成状况,以确定造模是否成功。造模成功后高脂模型组随机分组,分为高脂对照组、药物治疗组,每组8只。高脂对照组和药物治疗组均改为普通饲料,药物以灌胃法喂食。药物治疗组加用烟酸缓释胶囊0.05g(Kg.d-1),喂饲12周。用药前及用药12周后分别测血清总胆固醇(TC)、甘油三酯(TG)、HDL-C、及低密度脂蛋白胆固醇(LDL-C)。用药后门冬氨酸氨基转移酶(AST)测定,观察主动脉组织病理变化。结果:药物治疗组与高脂对照组相比较,TC、TG、LDL-C降低,HDL-C明显升高,差异有统计学意义(P<0.01)。药物治疗组与高脂对照组之间AST无统计学差异(P>0.05)。镜下观察见药物治疗组内膜增厚明显减轻,斑块内脂质和泡沫细胞数量减少,动脉粥样硬化斑块回缩;斑块面积/内膜面积比值、内膜厚度/中膜厚度比值,内膜厚度均明显降低,差异有统计学意义(P<0.01)。结论:烟酸缓释胶囊(锐旨)能够明显升高血清HDL-C,降低TC、TG、LDL-C;并阻止动脉粥样硬化进展,能使动脉粥样硬化斑块回缩,增厚的内膜变薄;并且其不良反应较少,安全性较高。

OBJECTIVE：To observe the effect of the modified release capsule of Nicotinic Acid on raising high density lipoprotein （HDL-C） and on arteriosclerosis plaque. METHODS：26 Japanese white rabbits were fed on normal diets for 2 weeks prior to experiment and then they were randomly divided into normal control group （n = 8） and high serum lipid model group （n = 18）. The normal control group （n = 8） was fed on normal diets for 22 weeks,and the high serum lipid model group （n = 18） was fed on high cholesterol diets （1% cholesterol and 8 % lard stearin were added in every 1 000 g normal diets）. 10 weeks later, 2 rabbits were randomly selected and sacrificed to observe the formation of arteriosclerosis plaques so as to make sure whether the modeling was successful or not. After successful modeling, the high serum lipid model group was randomly divided into high serum lipid control group （n = 8） and drug-intervention group （n = 8）,with both group fed with normal diets, while the drug-intervention group received additional modified release capsule of Nicotinic Acid （0.05 g· kg^-1 · d^-1 , ig） for 12 weeks. Serum levels of TC, TG, HDL-C and LDL-C were measured before treatment and at 12 weeks after treatment and AST were measured. The histopathologic change of the aorta was observed after treatment. RESULTS ： In Nicotinic Acid group compared with high serum lipid control group, serum levels of TC, TG and LDL-C were lower while the level of HDL-C was significantly higher, showing significant differences between the two groups （P 〈 0.01 ）. However, there was no significant difference between the two groups in AST level （ P 〉 0.05）. Under microscope, the thickening of intima was significantly lessened, the lipid within the plaque, the number of foam cells, the atheromatous area, the plaques area / intima area ratio and the intima thickness /media thickness ratio as well as the intima thickness were all significantly decreased in Nicotinic Acid group compared with high serum lipid control group,showing significant differences between the two groups （P 〈 0.01 ）. CONCLUSION：Modified release capsule of Nicotinic Acid could obviously increase serum HDL-C, decrease serum levels of TC, TG and LDL-C. Meanwhile, it could inhibit the progression of atherosclerosis, decrease the atheromatous area and reduce the thickness of the thickened intima yet with mild side effect but good safety.