普罗布考促进小鼠体内胆固醇逆转运的研究  

Probucol promotes reverse cholesterol transport from macrophage to feces in mice in vivo

作　　者：倪占玲[1] 赵水平[2] 董静[2] 吴智宏[2] 洪绍彩[2] 

机构地区：[1]河南省人民医院,河南郑州450003 [2]中南大学湘雅二医院心内科,湖南长沙410011

出　　处：《中国药理学通报》2007年第11期1444-1447,共4页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助(No30470705)

摘　　要：目的检测普罗布考干预后小鼠血清脂质,血清、肝脏及粪便中3H-胆固醇占经腹腔注射3H-胆固醇总量的百分比,探讨普罗布考对小鼠体内胆固醇逆转运的影响。方法32只C57BL/6小鼠随机分为4组,给予不同剂量普罗布考(0,0.1%,0.5%,1%W/W)添加饲料饲养4wk后,腹腔注射经ac-LDL及3H-胆固醇处理过的RAW264.7小鼠巨噬细胞悬液(0.5ml/鼠,细胞数达5.0×106,放射活性达6.2×106cpm),单笼喂养24h后取血,酶法测定血清脂质;收集血清、肝组织、0～24h粪便,分别用液闪计数仪测定3H-胆固醇含量(均以占注射总量百分比计);结果0.1%普罗布考干预4wk后总胆固醇(TC)较对照组降低34.3%,52.8%,(P<0.01),低密度脂蛋白胆固醇(LDL-C)及甘油三酯(TG)降低20%,22%,(P<0.05);0.5%和1%普罗布考降低TC,HDL-C47%,55%,(P<0.01);降低LDL-C和TG为32%,30%,(P<0.05)。腹腔注射巨噬细胞悬液24h后血清中3H-胆固醇含量呈剂量依赖性轻度降低,而肝脏和粪便中3H-胆固醇含量呈剂量依赖性明显升高,分别为20%～48%(P<0.05)和20%～84%(P<0.01)。结论普罗布考虽然降低HDL-C血浆水平,但是明显促进胆固醇的逆转运,加速了胆固醇经粪便的清除,利于动脉粥样硬化的防治。Aim To investigate the effect of probucol on reverse cholesterol transport from macrophage to feces in vivo,serum lipid profiles of mice were tested before and after probucol administration for 4 weeks,and the 3H-contents in serum,liver and feces in mice were quantitated after 24 hours intraperitoneally injected macrophages which were labeled with 3H cholesterol.Methods 32 C57BL/6 mice were treated with different probucol（0,0.1%,0.5%,1% W/W）in chow diet for 4 weeks,then these mice were injected intraperitoneally with RAW264.7 macrophages（0.5 ml·mice,cells 5.0×106 with 6.2×106 cpm）which were loaded with cholesterol by incubation with acetylated LDL,labeled with 3H-cholesterol.Serum profiles were quantitated by enzymatic method;serum and liver tissues were harvested at 24th hour,feces were collected（0~24 hs）,and all were analyzed for tracer counts（all were expressed as the percentage of the total injected counts per minute）.Results After 4 weeks 0.1% probucol administration,the levels of total cholesterol（TC）,high-density lipoprotein cholesterol（HDL-C）decreased markedly by 34.3%,52.8%,（P〈0.01）,low-density lipoprotein cholesterol（LDL-C）and triglyceride（TG）were reduced by 20% and 22%,respectively（P〈0.05）;0.5% and 1% probucol had the similar effects which reduced TC,HDL-C by 47% and 55%,（P〈0.01）,and decreased LDL-C and TG by 32% and 30%（P〈0.05）.3H-cholesterol was found in the plasma,liver,and feces,probucol led to modest lower 3H-cholesterol in plasma,and significantly higher 3H-cholesterol liver,and feces.The amount of 3H-tracer in the liver was 20%~48% higher（P〈0.05）and the 3H-tracer excreted into feces over 24 hours was 20%~84% higher（P〈0.01）in probucol-treated mice than in control mice.Conclusions Probucol markedly decreased HDL-C in plasma,while it promoted reverse transport from macrophage,accelerated clearance of cholesterol via feces,so it benefited the prevention of atherosclerosis.

关 键 词：普罗布考 胆固醇逆转运 ^3H-胆固醇 动脉粥样硬化 

分 类 号：R332[医药卫生—人体生理学] R344.81[医药卫生—基础医学]