甲氨蝶呤对动脉粥样硬化的作用及其机制

Effect and underlying mechanism of methotrexate on atherosclerosis

目的探讨甲氨蝶呤(MTX)对动脉粥样硬化的作用及其可能机制。方法36只兔建立高脂血症模型,随机均分为高脂饮食对照组(A组)、MTX干预组(B组)和瑞舒伐他汀干预组(C组)。检测各组血清TC、TG、HDL、LDL、IL-6和MMP-9水平变化,并于12周后取兔腹主动脉,光镜下观察血管形态和结构的变化,计算斑块面积占动脉内膜总面积的百分比。结果与A组相比,B组和C组IL-6、MMP-9水平降低[(70.37±5.77)ng/L和(72.42±4.74)ng/L vs.(115.78±11.40)ng/L、(43.08±3.35)μg/L和(44.60±4.24)μg/L vs.(64.38±5.11)μg/L](P<0.05),斑块面积/动脉内膜总面积减少[(30.76±4.80)%和(18.10±2.15)%vs.(54.90±6.59)%](P<0.05)。结论MTX可能通过降低炎症因子MMP-9、IL-6水平,从而达到抗动脉粥样硬化的作用。

Objective To investigate the effect and underlying mechanism of methotrexate(MTX)on the rabbits with atherosclerosis.Methods The hyperlipoidemia model was established in 36 rabbits,which then were equally randomized into three groups of A(model control),B(oral administration of MTX 4 mg/kg once a week)and C(oral administration of rosuvastatin 0.5 mg·kg-1·d-1).Serum levels of TC,TG,HDL,LDL,IL-6 and MMP-9 were measured.The abdominal aorta was taken after 12 weeks,and the changes of vascular morphology and structure were observed under light microscope.The percentage of plaque area accounting for total intimal area was calculated.ResultsCompared with group A,serum levels of IL-6 and MMP-9 were decreased[(70.37±5.77)ng/L and(72.42±4.74)ng/L vs.(115.78±11.40)ng/L and(43.08±3.35)μg/L and(44.60±4.24)μg/L vs.(64.38±5.11)μg/L],and the percentage of plaque area accounting for total intimal area was reduced[(30.76±4.80)%and(18.10±2.15)%vs.(54.90±6.59)%]in groups of B and C(P<0.05).Conclusion MTX has the effect on anti-atherosclerosis probably through down-regulating the secretions of IL-6 and MMP-9.