阿司匹林抑制兔腹主动脉粥样斑块破裂及MMP-2表达的研究

目的研究阿司匹林稳定粥样斑块的作用及其可能的作用机制。方法采用♂新西兰兔高脂饮食加腹主动脉内膜剥脱术制成高脂性动脉粥样硬化模型,然后给予阿司匹林5~20mg·kg-1治疗4wk,实验末诱发斑块破裂,运用图像分析方法测定斑块破裂处血栓形成的面积,利用光镜观察破裂斑块的形态学特征,采用免疫组化方法测定巨噬细胞的蛋白表达,原位杂交方法分别测定COX-2 mRNA和MMP-2 mRNA表达。结果阿司匹林5mg·kg-1和10mg·kg-1组可以抑制粥样斑块破裂处血栓的形成(P<0.01,P<0.05),且5mg·kg-1组的作用更明显;阿司匹林可以抑制斑块中泡沫细胞的形成和聚集,使纤维帽尤其是肩部区的结构保持得较为完整;阿司匹林5~10mg·kg-1可明显减少斑块内巨噬细胞数目(P<0.05),也能降低斑块中COX-2 mRNA的表达,且随着剂量的增加作用增强,在10~20mg·kg-1组的作用较为明显(P<0.05),还能明显降低粥样斑块中MMP-2 mRNA表达,但以阿司匹林5mg·kg-1组的作用较好(P<0.05)。结论阿司匹林可通过降低粥样斑块中MMP-2的表达增加动脉粥样斑块的稳定性。

Study of aspirin on inhibiting the atherosclerotic plaque rupture and MMP-2 expression of abdominal aorta in atherosclerotic rabbits

Aim To study the effects of aspirin on increasing the atherosclerotic plaque stability and its possible mechanisms.Methods The hyperlipidemic atherosclerotic model was generated in male New Zealand rabbits given high fat diet and endothelial abrasion of abdominal aorta.These rabbits were then treated with aspirin 5～20 mg·kg-1 for 4 weeks.At experimental end,the plaques were evoked into rupture by injection of Russell's viper venom and histamine.Areas of thrombosis on atherosclerotic aorta were determined by image analysis,morphologic character of plaque rupture was examined by light microscope,the protein expression of macrophages was detected by immunohistochemistry,and the mRNA expression of COX-2 and MMP-2 was determined by hybridization in situ,respectively.Results Aspirin at doses of 5～10 mg·kg-1 was able to inhibit thrombosis on atherosclerotic plaque(P<0.01,P<0.05),and the effect of 5 mg·kg-1 was better.Aspirin could inhibit foam cell formation and aggregation in atherosclerotic plaque,and keep the integrity of fiber cap and shoulder area.Aspirin could decrease the number of macrophages in 5 or 10 mg·kg-1 group(P<0.05),inhibit COX-2 mRNA expression in 10 or 20 mg·kg-1 group(P<0.05),and also decrease the MMP-2 mRNA expression in 5 mg·kg-1 group(P<0.05) in atherosclerotic plaque.Conclusion Aspirin was able to increase the stability of atherosclerotic plaque,which was associated with the reduction of MMP-2 expression in atherosclerotic plaque.