非洛地平对载脂蛋白E基因敲除小鼠动脉粥样硬化斑块及烟酰胺腺嘌呤二核苷酸氧化酶的影响  

Felodipine reduces atherosclerosis lesion and NAD(P)H oxidase in high cholesterol-diet apolipoprotein E knock-out mice

作　　者：姚瑞[1] 程翔[1] 廖玉华[1] 陈勇[1] 谢江娇[1] 余娴[1] 丁英俊[1] 唐婷婷[1] 

机构地区：[1]华中科技大学协和医院心内科,华中科技大学同济医学院心血管病研究所,心血管免疫实验室,武汉430022

出　　处：《临床心血管病杂志》2008年第9期698-701,共4页Journal of Clinical Cardiology

基　　金：国家重点基础研究发展计划(973计划)(No:2007CB512000)

摘　　要：目的:探讨钙通道阻断剂(CCB)非洛地平对载脂蛋白E基因敲除(apoEKO)小鼠动脉粥样硬化斑块及烟酰胺腺嘌呤二核苷酸[NAD(P)H]氧化酶的影响。方法:apoEKO小鼠随机分为普通饮食组、高胆固醇饮食组、高胆固醇饮食加非洛地平组。无创血压系统测小鼠血压;内眦动脉取血检测血清TC和TG水平;冷冻切片光镜下定位主动脉根部,油红O染色评估斑块大小;实时定量PCR和Western blot方法检测主动脉中NAD(P)H氧化酶亚基p47phox和Rac-1表达。结果:高胆固醇饮食组小鼠血压没有明显变化,血脂明显升高(P<0.01),且斑块面积明显高于普食组(P<0.01);非洛地平可以明显减小斑块面积(P<0.01),同时还可以降低NAD(P)H氧化酶亚基p47phox和Rac-1表达(P<0.01)。结论:非洛地平可能通过阻断氧化应激反应抑制动脉粥样硬化发生发展。Objective：To investigate the potential effects of felodipine, a calcium channel blocker, on the atherosclerosis lesion and NAD（P）H oxidase in high cholesterol-diet （HCD） apolipoprotein E knock-out （apoE KO） mice. Method：Aduh male apoE KO mice were divided into normal diet （ND） group, HCD group, and HCD plus felodipine group. Blood pressure of mice was measured by a kind of non-invasive tail cuff system. The plasma total cholesterol and triglyeeride concentration from angular artery were measured by autoanalyzer. Atherosclerotic lesion area in arotic root was evaluated by oil red O staining. NAD（P）H oxidase suhunits were measured by Realtime reverse-transcription polymerase chain reaction （PCR） and western blot. Result：The apoE KO mice with HCD was associated with a marked increase in plasma lipid levels, atherosclerotic lesion area, as well as the expressions of NAD（P）H oxidase subunits p^47phox and Rac 1. These changes were suppressed in mice by treating with felodipine, with no significant change in systolic blood pressure and plasma lipid levels. Conclusion： The results suggest that felodipine can attenuate atherosclerosis, and this effect is in part related to inhibition of oxidative stress.

关 键 词：动脉粥样硬化 非洛地平 氧化应激 

分 类 号：R541.4[医药卫生—心血管疾病]