[孟鲁司特对高胆固醇血症兔模型动脉粥样硬化及单核细胞趋化蛋白-1表达的影响。]

[Effects of montelukast on atherosclerosis and monocyte chemoattractant protein-1 expression in ahypercholesterolemic rabbit model.].

作者信息

Ge Song, Liu De-Zhi, Zhou Guang-Yi, Hu Wei, Chen Hong-Bing, Xiao Guo-Dong, Zhu Wu-Sheng, Xu Ge-Lin, Liu Xin-Feng

机构信息

Department of Neurology, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, China.

出版信息

Zhonghua Xin Xue Guan Bing Za Zhi. 2009 Mar;37(3):257-61.

PMID:19781153

Abstract

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 mgxkg(-1)xd(-1), beginning at 8(th) weeks for 4 weeks, n = 10) and montelukast group (1 mgxkg(-1)xd(-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 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 hypercholesterolemic rabbit model which might be attributed to its anti-inflammatory effects.

摘要

目的

在高胆固醇血症兔模型中研究孟鲁司特对动脉粥样硬化及单核细胞趋化蛋白-1表达的影响。

方法

34只雄性新西兰白兔随机分为四组，包括正常对照组（n = 6）、安慰剂组（n = 8）、阿托伐他汀组（1.5 mg·kg⁻¹·d⁻¹，第8周开始给药，持续4周，n = 10）和孟鲁司特组（1 mg·kg⁻¹·d⁻¹，第8周开始给药，持续4周，n = 10）。除正常对照组外，其余兔子均给予高胆固醇饮食12周。在干预后0、8和12周测量血脂。检测内膜/中膜比值、内膜中巨噬细胞或平滑肌细胞百分比以及MCP-1 mRNA的表达。

结果

安慰剂组出现动脉粥样硬化，阿托伐他汀或孟鲁司特治疗显著减少了新生内膜（0.32±0.12和0.34±0.10对比1.12±0.36，P < 0.05）和巨噬细胞含量[（9.8±4.6）%和（11.2±3.7）%对比（34.6±8.8）%，P < 0.05]，增加了平滑肌细胞含量[（18.6±6.9）%和（19.2±8.6）%对比（5.2±2.3）%，P < 0.05]，并抑制了MCP-1 mRNA的表达（0.42±0.08和0.40±0.06对比2.36±0.48，P < 0.01）。孟鲁司特具有与阿托伐他汀相似的抗动脉粥样硬化作用，但对血脂无影响。