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.