非洛地平对高胆固醇饮食载脂蛋白E基因敲除小鼠动脉粥样硬化的影响

Effects of felodipine on atherosclerosis in high cholesterol-diet apolipoprotein E knock-out mice

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(ApoE KO)小鼠动脉粥样硬化斑块的影响。方法:ApoE KO小鼠随机分为普食组、高胆固醇饮食组、高胆固醇饮食+非洛地平组(n=15),分别予蒸馏水或非洛地平5mg·kg-1·d-1灌胃12周。无创血压系统测小鼠血压;内眦动脉取血检测血清胆固醇和甘油三酯水平;冰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 blotting方法检测主动脉中炎症因子表达。结果:高胆固醇饮食组小鼠血脂明显升高(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),同时还可以降低肿瘤坏死因子-α(TNF-α)、单核细胞趋化因子-1(MCP-1)和血管细胞黏附因子-1(VCAM-1)的表达。结论:钙通道阻断剂非洛地平可能通过抑制炎症反应,降低炎症因子表达,从而达到抑制动脉粥样硬化发生发展的目的。

AIM： To investigate the potential effects and molecular mechanisms of a calcium channel blocker felodipine on the process of atherosclerosis in high cholesterol - diet （HCD） apolipoprotein E knock - out （ ApoE KO） mice. METHODS： Adult male ApoE KO mice were given normal diet （ND） or HCD and randomized to normal diet or felodipine 5 mg·kg^-1·d^-1 for 12 weeks. Systolic blood pressure was measured by a kind of non -invasive tail cuff system in conscious condition. The plasma total cholesterol and triglyceride concentration were measured by autoanalyzer. Atherosclerotic lesion area in arotic root was evaluated by oil red O staining. Inflammatory cytokines were measured by real- time reverse -transcription polymerase chain reaction （PCR） and Western blotting. RESULTS： The ApoE KO mice with HCD were associated with a marked increase in plasma lipid levels, atherosclerotic lesion area, as well as the expressions of tumor necrosis - or, monocyte chemoattactant protein - 1 and vascular cell adhesion molecule - 1. These changes were suppressed in mice that were treated with felodipine 5 mg·kg^-1·d^-1 for 12 weeks concomitant with HCD administration. CONCLUSION： The results suggest that felodipine attenuates atherosclerosis. This effect is in part related to inhibition of inflammatory response which leads to the decrease in the expression of inflammatory cytokines.