罗格列酮对动脉粥样硬化兔高密度脂蛋白的影响  

Effect of peroxisome proliferator activated receptor-γ agonist on high density lipoprotein function in artherosclerosis rabbits

作　　者：范永臻[1] 郭志刚[1] 王振坤[1] 赖文岩[1] 屠燕[1] 黄邹琴[2] 

机构地区：[1]南方医科大学南方医院心内科,广州市510515 [2]广州医学院附属肿瘤医院,510095

出　　处：《实用医学杂志》2010年第9期1508-1512,共5页The Journal of Practical Medicine

基　　金：广东省社会发展领域科技计划项目(编号:2008B030301158);南方医科大学南方医院院长重点基金(编号:2008A003)

摘　　要：目的:观察过氧化酶体增殖物激活型受体γ(PPARγ)激动剂罗格列酮对动脉粥样硬化(AS)兔高密度脂蛋白(HDL)受体ATP结合盒转运子A1(ABCA1)及细胞内胆固醇转出率的影响,探讨罗格列酮对AS兔HDL功能的影响。方法:18只新西兰大白兔随机分为3组。(1)正常对照组,普通饲料喂养;(2)动脉粥样硬化组(AS组),单纯喂食高胆固醇饮食;(3)罗格列酮组,在单纯高胆固醇饮食的基础上,予以灌服罗格列酮0.5mg/(kg·d)。喂养12周后取血以酶法测定血清脂质;利用流式细胞术分别检测肝细胞、腹腔细胞ABCA1的表达量,液闪计数仪检测细胞溶解物及细胞内胆固醇转出率。结果:与对照组相比,AS组血浆总胆固醇、低密度脂蛋白胆固醇、甘油三酯、高密度脂蛋白胆固醇(HDL-C)、非高密度脂蛋白(NHDL-C)水平显著升高;与AS组相比,罗格列酮组血浆HDL-C水平显著升高,NHDL-C显著降低;罗格列酮组腹腔巨噬细胞、肝细胞[3H]胆固醇转出率及其ABCA1表达明显增加。结论:罗格列酮不仅能显著提高HDL-C血浆水平,而且通过增加ABCA1表达,改善了HDL颗粒功能,促进AS兔巨噬细胞、肝细胞内胆固醇流出,具有抗动脉粥样硬化作用。Objective To investigate the effect of rosiglitazone, peroxisome proliferator activated receptor- γ agonist, on reverse cholesterol transport and to research its mechanism of anti-atherosclerosis in artheroselerosis （AS） rabbits. Methods Eighteen rabbits were randomly divided into three groups ： （ 1 ） control group （n = 6） ： only normal diet for 12 weeks ; （2）AS group： maintained cholesterol diet for 12 weeks： （3） rosiglitazone group： the same cholesterol diet plus rosiglitazone 0.5 mg/（kg·d） for 12 weeks. Expressions of ATP-binding cassette transporter A1 （ABCA1） in peritoneal macrophages and hepatocytes were evaluated by flow cytometry, and the rate of cholesterol efflux from those cells were determined by measuring release of radioactivity from [^3H ]-cholesterol prelabeled cells into medium by liquid scintillation spectrometry. Results Compared with the AS group, in rosiglitazone group, expressions of ABCAI and rate of [^3H] cholesterol efflux were increased, levels of serum high density lipoprotein cholesterol （HDL-C） were also increased, while levels of serum non-high density lipoprotein cholesterol （NHDL-C） were decreased. There were no significant differences in NHDL-C levels. Conclusions Rosiglitazone can significantly increase level of plasma HDL-C, improve the HDL function, and promote cholesterol efflux of hepatic cells and peritoneal macrophages in hyperlipidemia rabbits. It has antiatherosclerosis effect.

关 键 词：高脂血症 罗格列酮 胆固醇逆转运 ATP结合盒转运子A1 过氧化酶体增殖物激活型受体γ 

分 类 号：R543[医药卫生—心血管疾病]