摘要
目的:探讨降胆固醇及抗氧化药物普罗布考对动脉粥样硬化形成过程中高密度脂蛋白(HDL)代谢的影响。方法:利用普罗布考(0.5%,w/w)给药于载脂蛋白E(apoE)和清道夫受体BI(SRBI)双基因敲除(DKO)鼠6周,血浆经快速蛋白液相色谱(FPLC)分离后检测各脂蛋白胆固醇水平,酶法测定HDL相关抗氧化酶对氧磷酯酶1(PON1)和血小板活化因子-乙酰水解酶(PAF-AH)活性,并比较普罗布考对DKO鼠粥样硬化斑块形成的影响。结果:普罗布考降低DKO鼠血浆总胆固醇水平56%,同时使其异常大分子的HDL出现部分颗粒大小正常化,PON1及PAF-AH活性明显增高,粥样斑块损伤明显减轻。结论:普罗布考在apoE/SR-BI DKO鼠的抗粥样硬化作用与其保护HDL正常性质与功能有关。
To investigate the effect of a lipid-lowering and antioxidation drug probucol on HDL metabolism and atherogenesis in the scavenger receptor class BI （SR-BI）/apolipoprotein E （apoE） double knockout （DKO） mice. Methods： A normal diet either with or without 0. 5%（wt/ wt） probucol supplementation was given to SR-BI/apoE DKO mice for six weeks. Lipoprotein cholesterol was fractionated by gel filtration on fast protein liquid chromatography （FPLC） system. Serum total cholesterol and free cholesterol, triglyceride levels, paraoxonase 1 （PON1） and platelet-activating factor acetylhydrolase （PAF-AH） activity were determined enzymatically, and oil red O-stained crosssections of proximal aortas was used to measure atherosclerotic lesion area. Results： Probucol treatment lowered by 56% the level of serum total cholesterol, decreased the abnormally large HDL particles and induced the appearance of a small normal-size HDL peak in DKO mice. The activities of serum PON1 and PAF-AH in DKO mice with probucol were significantly increased than those in untreated DKO mice （P〈0. 001）. Administration of probucol dramatically protected from aortic root atherosclerosis with 85 % decrease in mean lesion area in DKO mice. Conclusion： The anti-atherogenic effect of probucol in apoE/SR-BI DKO mice is in part associated with lowering HDL particle size and protection of lipoproteins against oxidative stress.
出处
《武汉大学学报（医学版）》
CAS
2006年第3期291-294,322,F0002,共6页
Medical Journal of Wuhan University
