普罗布考对动脉粥样硬化兔HDL功能的影响及其调控机制  

The effect and mechanism of probucol on HDL function in atherosclerotic rabbits

作　　者：王振坤[1] 郭志刚[1] 范永臻[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510515 [2]广州医学院附属肿瘤医院,广州510095

出　　处：《广东医学》2010年第5期533-536,共4页Guangdong Medical Journal

基　　金：广东省社会发展领域科技计划项目(编号:200813030301158);南方医科大学南方医院院长重点基金(编号:2008A003)

摘　　要：目的观察普罗布考对动脉粥样硬化兔巨噬细胞、肝细胞HDL功能的影响,并进一步探讨普罗布考抗动脉粥样硬化的机制。方法18只新西兰大白兔随机分为:(1)正常对照组(n=6):给予普通饮食喂养;(2)动脉粥样硬化组(n=6):饲以高脂饲料;(3)普罗布考组(n=6):在饲以高脂饮食基础上给予普罗布考[400mg/(kg·d)]。12周后取血以酶法测定血脂;利用流式细胞仪检测腹腔巨噬细胞、肝细胞细胞表面ABCA1、SR-BⅠ表达量;液闪计数仪检测其[3H]胆固醇转出率。结果实验12周后,普罗布考组血清总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、非高密度脂蛋白(NHDL-C)水平明显下降。普罗布考上调动脉粥样硬化兔腹腔巨噬细胞及肝细胞ABCA1及SR-BⅠ蛋白质表达水平。普罗布考组腹腔巨噬细胞、肝细胞[3H]胆固醇转出率较动脉粥样硬化组明显上升。结论虽然普罗布考降低HDL-C,但是其通过上调腹腔巨噬细胞、肝细胞SR-BⅠ及ABCA1的表达及增加其[3H]胆固醇转出率,改善HDL功能,具有促进动脉粥样硬化兔胆固醇逆转运(RCT)作用。Objective To analyze the effect of probucol on HDL function and the its anti-atherosclerosis mechanism in atherosclerotic rabbits. Methods Eighteen rabbits were randomly assigned into three groups：（1） control group （n=6）：normal diet for 12weeks; （2） atherosclerotic group：cholesterol diet of 12 weeks; （3） probucol group：cholesterol diet plus probucol （400mg/ （kg·d）） for 12 weeks. Flow cytometry and liquid scintillation spectrometry were used to measure the expressions of ABCA1 and SR-B,and cholesterol efflux rates,respectively,in peritoneal macrophages and hepatocytes. Results Compared with atherosclerotic group,the levels of serum total cholesterol （TC）,low-density lipoprotein cholesterol （LDL-C）,high density lipoprotein cholesterol （HDL-C） and non-high-density lipoprotein cholesterol （NHDL-C） in probucol group were significantly reduced. In peritoneal macrophages and hepatocytes,the ABCA1 and SR-BⅠ expression and [3H] cholesterol efflux rates significantly increased in probucol group compared with that in atherosclerotic group. Conclusion Via up-regulating SR-Bl and ABCA1 expression and increasing cholesterol efflux rates in peritoneal macrophages and hepatocytes,probucol improves HDL function and reverse cholesterol transport （RCT）.

关 键 词：普罗布考 结合盒转运体A1 B族Ⅰ型清道夫受体 高密度脂蛋白 动脉粥样硬化 

分 类 号：R972.6[医药卫生—药品]