阿托伐他汀抗动脉粥样硬化的分子机制研究

目的:研究阿托伐他汀抗动脉粥样硬化(atherosclerosis,AS)作用的分子机制。方法:制备大鼠AS模型,治疗组以阿托伐他汀干预4周,观察各组大鼠主动脉AS的病理改变,并检测其血浆溶血磷脂酸(lysophosphatidic acid,LPA)水平以及主动脉壁肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、基质金属蛋白酶9(Matrix Metalloproteinase-9,MMP-9)的活性和表达。结果:AS模型组的各项指标水平均明显升高,同时主动脉出现典型AS斑块。阿托伐他汀治疗组大鼠的上述水平同AS模型组相比较均有明显改善,相应主动脉AS的程度也减轻。结论:LPA参与了AS的形成过程,其机制可能与其促进炎性因子释放增多以及活性表达增强有关。阿托伐他汀不仅通过减低TNF-α表达以及MMP活性达到抗炎作用,而且通过降低LPA水平起到抗AS作用。

Molecular mechanisms for atorvastatin against atherosclerosis

Objective: To investigate the anti-atherosclerosis mechanisms of atorvastatm. Methods: AS model in Wistar rat was devoleped by giving wistar rats a high-fat diet and vitamin D3 injection. Atorvastatin was given in study group rat when the model was accomplished, and pathological change of the aortic artherosclerotic plaque were observed and the level of plasma LPA, the expression of TNF-a and the activity of MMP-9 in aorta wall were detected in control, AS model and study group respectively. Result: Typical AS plaques were observed in the aorta in AS model group and a more lightly lesion in study group. The level of LPA, TNF-a and MMP-9 in aorta wall were significantly higher in model group than that in control group, while they were obviously improved in study group. Conclusion: The expression of TNF-a and the activity of MMP-9 in aortic wall were increased markedly in AS rats. It may be a molecular mechanism of LPA that accelerate AS. Atorvastatin not only inhibit inflammatory responses but also decrease the level of LPA in AS rats and interfere pathogenesis of AS.