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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 被引量：3

Effects of montelukast on atherosclerosis and monocyte chemoattractant protein-1 expression in a hypercholesterolemic rabbit model
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摘要 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（1．5mg·kg^-1·d^-1）和孟鲁司特（1mg·kg^-1·d^-1），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-1mRNA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-1mRNA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。 Objective To investigate the effects of montelukast on atherosclerosis and monocyte chemoattractant protein-1 expression in a hypercholesterolemic rabbit model. Methods Thirty four male New Zealand white rabbits were randomized into four groups including normal control group （ n = 6）, placebo group （n = 8 ）, atorvastatin group （1.5 mg·kg^-1·d^-1, beginning at 8th weeks for 4 weeks, n = 10 ） and montelukast group （ 1 mg·kg^-1·d^-1 , beginning at 8^th weeks for 4 weeks, n = 10）. Rabbits except those 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 Atherosclerosis was evidenced in placebo group and atorvastatin or montelukast treatment significandy 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 hypercholesterolemic rabbit model which might be attributed to its anti-iaflammatory effects.
作者 葛颂 刘德志 周广怡 胡伟 陈红兵 肖国栋 朱武生 徐格林 刘新峰
机构地区 南京大学临床学院南京军区南京总医院神经内科
出处 《中华心血管病杂志》 CAS CSCD 北大核心 2009年第3期257-261,共5页 Chinese Journal of Cardiology
基金 中国博士后科学基金资助项目（20080431415）
关键词 动脉粥样硬化 白三烯拮抗剂 降血脂药 趋化因子CCL2 Atherosclerosis Receptors, leukotriene Antilipemic agents Chemokine CCL2
分类号 R686 [医药卫生—骨科学]
  • 相关文献

参考文献23

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二级参考文献29

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共引文献14

同被引文献24

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引证文献3

二级引证文献17

中华心血管病杂志
2009年 第3期

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