孟鲁司特对兔动脉粥样硬化的作用及其对单核细胞趋化蛋白-1表达的影响

目的 探讨选择性半胱胺酰白三烯受体1拮抗剂孟鲁司特对兔动脉粥样硬化的作用及其相关机制.方法 34只雄性新西兰大白兔随机分成4组:空白对照组(n=6)、安慰剂对照组(n=8)、阿托伐他汀组(n=10)和孟鲁司特组(n=10).空白对照组给予普通饮食,其余3组均给予高脂饮食.8周后,阿托伐他汀组和孟鲁司特组分别给予阿托伐他汀(1.5 mg·kg·d)和孟鲁司特(1 mg·kg·d),继续高脂饮食4周.饮食干预前和干预后8、12周测血脂.12周后,检测升主动脉内/中膜比,分析内膜中巨噬细胞和平滑肌细胞(SMC)面积百分比以及斑块中单核细胞趋化蛋白-1(MCP-1)mRNA的表达.结果 安慰剂对照组内膜明显增生,内膜中含有大量巨噬细胞和少量SMC,MCP-1 mRNA表达增加.与安慰剂组比较,阿托伐他汀和孟鲁司特组的内/中膜比(0.32±0.12和0.34±0.10比1.12±0.36,均P<0.05)和内膜中巨噬细胞[(9.8±4.6)%和(11.2±3.7)%比(34.6±8.8)%,均P<0.05]较低,SMC的含量[(18.6±6.9)%和(19.2±8.6)%比(5.2±2.3)%,均P<0.05]较高,MCP-1 mRNA表达(0.42±0.08和0.40±0.06比2.36±0.48,均P<0.01)较低.孟鲁司特具有和阿托伐他汀相似的抗动脉粥样硬化作用,但阿托伐他汀可以降低总胆固醇、甘油三酯和低密度脂蛋白胆固醇,而孟鲁司特对血脂无影响.结论 孟鲁司特具有抗动脉粥样硬化作用,其机制可能在于抑制动脉粥样硬化的炎症反应.

Effects of montelukast on atherosderosis and monocyte chemoattractant protein-1 expression in a hypercholesterolemic rabbit model

Objective To investigate the effects of montelukast on atherescleresis and monocyte chemoattractant protein-1 expression in a hyperchulesterolemic rabbit modeL Methods Thirty four male New Zealand white rabbits were randomized into four groups including normal control group (n=6), placebo in normal control group were fed a high cholesterol diet for 12 weeks. Serum lipids were measured at 0, 8 and 12 weeks after intervention. The intima/media ratio, percentages of macrophages or smooth muscle cells in intima and the expression of MCP-1 mRNA were examined. Results Atheresclerosis was evidenced in placebo group and atorvastatin or montelukast treatment significantly reduced neointima (0.32±0.12 and 0.34±0.10 vs. 1.12±0.36,P<0.05) and macrophage content [(9.8±4.6) % and(11.2±3.7) % vs. (34.6±8.8)%,P<0.05], increased SMC content [(18.6±6.9)% and(19.2±8.6)% vs. (5.2±2.3) %, P<0.05] and inhibited expression of MCP-1 mRNA (0.42±0.08 and 0.40±0.06 vs. 2.36±0.48 ,P<0.01). Montelukast had similar anti-atherogenetic effects as atorvastatin but had no influence on plasma lipids. Conclusions Montelukast could attenuate atherosclerosis in this hyperchulesterolemic rabbit model which might be attributed to its anti-inflammatory effects.