普罗布考对高脂喂养LDLR^(-/-)小鼠动脉粥样硬化的影响及机制研究  

Effect of Probucol on Atherosclerosis in LDLR^(-/-) Mice Fed a High-fat Diet

作　　者：朱洪[1] 马鑫[1,2] 申程[1,3] 董震[4] 刘湘玮[1] 王鹏[1,3] 葛均波[1,2] 孙爱军[1,2] 

机构地区：[1]复旦大学附属中山医院上海市心血管病研究所,上海市200032 [2]复旦大学生物医学研究院,上海市200032 [3]山东大学心内科,山东省济南市250012 [4]复旦大学附属华山医院心内科,上海市200032

出　　处：《中国分子心脏病学杂志》2014年第2期860-863,共4页Molecular Cardiology of China

基　　金：国家重点基础研究发展计划(973)(2011CB503905)

摘　　要：目的探讨普罗布考对高脂喂养LDLR-/-小鼠动脉粥样硬化的影响并初步阐明其作用机制。方法 14只8周龄LDLR-/-雄性小鼠,予以高脂喂养4周后随机分为高脂组(继续高脂饮食,n=7)和普罗布考组(高脂加0.5%普罗布考,n=7),喂养14周后处死,检测血浆中甘油三酯(TG)、总胆固醇(TG)和高密度脂蛋白胆固醇(HDL-C)水平;取主动脉进行油红O染色观察斑块生长情况;制作主动脉根部冰冻切片,分别进行油红O、Masson染色,检测主动脉根部斑块面积和胶原含量;ELISA检测血浆中炎症因子IL-12p70水平。结果普罗布考组小鼠血浆TG、HDL-C显著低于高脂组(P均<0.01),TG无显著改变(P>0.05);油红O染色结果显示,两组间主动脉斑块占主动脉比例无显著差异(P>0.05),但普罗布考组小鼠主动脉根部斑块面积显著高于高脂组(P<0.01);Masson染色结果显示,普罗布考组小鼠主动脉根部斑块中胶原比例显著高于高脂组(P<0.01);ELISA结果显示,普罗布考组小鼠血浆IL-12p70水平显著低于高脂组(P<0.05)。结论普罗布考可降低高脂喂养的LDLR-/-小鼠血浆TG、HDL-C和IL-12p70水平,促进主动脉根部斑块形成,但增加主动脉根部斑块中胶原含量。Objective To assess the effect of probucol on atherosclerosis in LDLR-/- mice. Methods Fourteen eight-week old male LDLR-/- mice were fed with high-fat diet for four weeks. Then the mice were randomly divided into two groups： high-fat group （n=7） or probucol group （high-fat diet plus 0.5% probucol, n - 7）. After 14 weeks of diet, mice were killed, blood was collected and plasma TG, TC and HDL-C concentrations were measured. Aorta plaques were stained with oil red O and plaque area was analysed. Atherosclerosis plaque in aorta root was made into frozen sections, plaque area and collagen content was analysed by oil red O and Masson staining, respectively. Plasma IL-12p70 concentration was detected by ELISA. Results Plasma levels of TC and HDL-C in the probucol group significantly decreasd compared with those in the high-fat group（all P〈0. 01）, whereas TG showed no significant change between two groups（P〉0.05）. Oil red O staining showed no significant change in aorta plaque area（P〉0.05）, but in aorta root, probucol group showed bigger plaque compared with high-fat group（P〈0.01）. Collagen content in probucol group significant increased compared with high-fat group（P〈0.01）. And ELISA result showed decreased plasma IL-12p70 concentration in probucol group（P〈0.05） Conclusion Probucol may reduce the levels of plasma TC, HDL-C and IL-12p70 and promote the progression of atherosclerosis lesion in aorta root in LDLR-/- mice fed a high-fat diet. However, Probucol may accelerate collagen deposition, which means higher aorta root plaque stability.

关 键 词：普罗布考 动脉粥样硬化 胆固醇 胶原 

分 类 号：R543.5[医药卫生—心血管疾病]