阿托伐他汀对动脉粥样硬化大鼠主动脉内膜增生的影响及与树突细胞分布的关系

Association of distribution of dendritic cells with intima hyperplasia in mice with atherosclerosis and the intervention of Atorvastatin

目的探讨动脉粥样硬化(AS)大鼠树突细胞(DCs)在外周血、动脉壁分布情况与主动脉内膜增生的关系以及阿托伐他汀的干预效应。方法 SD大鼠30只分组饲养12 w后,测定主动脉内膜增生情况。分别取外周血、动脉壁组织,并制备组织单细胞悬液,应用流式细胞仪检测DCs比例情况。用荧光定量RT-PCR技术检测DCs的CX3CR1表达情况。结果 AS大鼠内膜较正常对照大鼠内膜增生明显(P<0.001),其外周血DCs分布明显减少(P<0.05)且主动脉内DCs比例明显升高(P<0.05)。应用阿托伐他汀后AS大鼠内膜增生明显减轻(P<0.05),其外周血DCs分布增多(P<0.001)且主动脉壁内DCs比例明显降低(P<0.001)。AS大鼠DCs的CX3CR1基因相对表达量较对照组明显升高(P<0.05),应用阿托伐他汀后CX3CR1基因相对表达量减少(P<0.05)。结论 AS大鼠主动脉内膜增生与DCs比例变化有关,DCs在AS大鼠主动脉内膜增生、管壁粥样硬化形成中可能起重要作用。阿托伐他汀可能通过抵制DCs向动脉内膜迁移,降低局部免疫炎症反应,此作用可能与DCs下调CX3CR1基因表达有关。

Objective To investigate the association of distribution of dendritic cells（DCs） in the peripheral blood and arterial wall with intima hyperplasia in atherosclerotic mice and the intervention effects of Atorvastatin in vivo.Methods 30 mice were divided into three groups and loaded with different diet for 12 weeks.Peripheral blood and arterial wall were collected to prepare for cell suspensions,the proportions of DCs were determined by flowcytometry.The expression of CX3CR1 of DCs was measured by quantitative RT-PCR.Results Compared with control group,the tunica intimal hyperplasia was more obvious in atherosclerotic mice（P0.001）,while DCs decreased significantly in the peripheral blood（P0.05）,but increased in the arterial wall（P0.05）.With usage of Atorvastatin,the tunica intimal hyperplasia was decreased obviously compared with that of atherosclerotic mice（P0.05）,while DCs in the peripheral blood increased significantly（P0.001）,but decreased in the arterial wall（P0.001）.CX3CR1 expression of DCs were increased significantly in atherosclerotic mice（P0.05）,but decreased after usage of Atorvastatin（P0.05）.Conclusions Changes in the distribution of DCs are closely associated with intima hyperplasia of atherosclerotic mice,which suggests the involvement of DCs in the formation of atherosclerosis.Correlating with CX3CR1 decreased expression,Atorvastatin has a profound inhibitory effect on immigration of DCs,which may be one of its mechanisms in the prevention of atherosclerosis.