普罗布考通过调控ABCA1、SR-BⅠ、ABCG5、ABCG8表达及抗炎作用抑制高胆固醇血症兔动脉粥样硬化(英文)  

Probucol Inhibits Atherosclerosis by Regulating ABCA1, SR-BⅠ, ABCG5 and ABCG8 Expression and Anti-inflammatory Effects in Hypercholesterolemic Rabbits

作　　者：崔立宝[1,2] 于小华[1] 蒋崇辉 唐雅玲[1] 欧阳新平[1] 何平平[1] 吕运成[1] 姚峰[1] 张敏[1] 唐朝克[1] 

机构地区：[1]南华大学心血管研究所,湖南省动脉硬化学重点实验室,南华大学生命科学研究中心,湖南省分子靶标新药研究协同创新中心,衡阳421001 [2]衡阳市中心医院药剂科,衡阳421001

出　　处：《生物化学与生物物理进展》2015年第9期866-876,共11页Progress In Biochemistry and Biophysics

基　　金：supported by grants from The National Natural Sciences Foundation of China(81070220,81170278)~~

摘　　要：作为一种有效的降脂药物,普罗布考能够降低血浆高密度脂蛋白胆固醇(HDL-C)水平并抑制动脉粥样硬化,但其机制尚未完全阐明.本研究的目的旨在进一步阐明普罗布考降脂及抗动脉粥样硬化的机理.将新西兰白兔随机分为4组:正常饮食组、正常饮食+普罗布考组、高脂饮食组(HFD组)、高脂饮食+普罗布考组(HFD+P组).结果显示,处理7周后,与HFD组比较,H FD+P组动脉粥样硬化病变程度、肝脏脂质蓄积明显减轻,血浆甘油三脂、总胆固醇、低密度脂蛋白胆固醇及HDL-C水平降低,肝脏中清道夫受体-BⅠ(SR-BⅠ)以及肝脏与小肠中三磷酸腺苷结合盒转运体(ABC)G5(ABCG5)、ABCG8表达上调,肝脏中A BCA1表达下调,主动脉弓与血浆肿瘤坏死因子α、白介素1、白介素6、单核趋化蛋白1水平降低.这些结果表明普罗布考的抗动脉粥样硬化作用可能与其调控A BCA1、SR-BⅠ、ABCG5、ABCG8表达及抑制促炎介质的分泌有关.Probucol is a potent hypolipidemic drug that decreases plasma high-density lipoprotein cholesterol （HDL-C） levels but attenuates atherosclerosis. However, the detailed mechanisms are not fully understood. The aim of this study was to explore the molecular mechanisms of the HDL-C-lowering and antiatherogenic effects of probucol. New Zealand white rabbits were randomly divided into normal diet group, normal diet＋probucol group, high fat diet （HFD） group and HFD＋probucol （HFD＋P） group. After 7 weeks of treatments, the extent of the atherosclerotic lesions, hepatic lipid accumulation and plasma levels of triglycerides, total cholesterol, low-density lipoprotein cholesterol and HDL-C were significantly reduced in HFD＋P group as compared to HFD group. Probucol effectively inhibited down-regulation of hepatic scavenger receptor class B type I （SR-B I ） expression, and ATP-binding cassette （ABC） transporters G5 （ABCG5） and G8 （ABCG8） expression in the liver and small intestine induced by HFD but further promoted HFD-induced reduction in hepatic ABC transporter A1 （ABCA1） expression. In addition, probucol also significantly prevented HFD-induced increases of turnor necrosis factor-a, interleukin-1, interleukin-6 and monocyte chemotactic protein-1 levels in the aortic arch and plasma. Thus, our data provide strong evidence that probucol alleviates atheroselerosis through regulating ABCA1, SR-B I, ABCG5 and ABCG8 expression and inhibiting the secretion ofproinflammatory cytokines in hypercholesterolemic rabbits.

关 键 词：普罗布考 动脉粥样硬化 高密度脂蛋白胆固醇 三磷酸腺苷结合盒转运体A1 清道夫受体-BⅠ 三磷酸腺苷结合盒转运体G5 三磷酸腺苷结合盒转运体G8 炎症 

分 类 号：R363[医药卫生—病理学]