阿托伐他汀对巨噬细胞胆固醇外流的影响

Regulation of macrophage cholesterol efflux by atorvastatin

目的通过研究阿托伐他汀对巨噬细胞的肝X受体(LXR)及其下游的一些目的基因的表达和胆固醇外流的影响,探讨他汀类药物对LXR信号系统的作用。方法分离人外周血的单核细胞,并转化为巨噬细胞。在阿托伐他汀的作用下,观察巨噬细胞的载脂蛋白A-Ⅰ(apoA-Ⅰ)介导的胆固醇外流的变化和LXR以及其下游一些目的基因的mRNA表达。结果阿托伐他汀显著影响巨噬细胞中一些涉及胆固醇代谢及炎症反应的基因的表达,同时apoA-Ⅰ介导的胆固醇外流也受到影响,表现为增强胆固醇的外流。结论巨噬细胞在阿托伐他汀的作用下,胆固醇外流增强,这种效应与阿托伐他汀上调LXR及其下游的影响胆固醇代谢的目的基因有关,同时,也抑制一些炎症反应的基因的表达。提示他汀类药物的治疗作用,与其影响巨噬细胞LXR信号途径有关,从而影响泡沫细胞的形成。

Objective To investigate the effects of atorvastatin on the gene expression of liver X receptor alfa（LXRα） and its downstream signaling system and on the cholesterol efflux of human macrophages. Methods Human monocytes were isolated and were induced to transform to macrophages.ApoA-I induced human monocyte-derived macrophage cholesterol efflux and gene expression of LXRα and its downstream signaling system were observed under the use of atorvastatin. Results Preincubation of human monocyte-derived macrophages with atorvastatin,dose dependently（1-2 μmol/L） stimulated cholesterol efflux induced by apoA-I.Atorvastatin increased the gene expression of LXRα and its downstream signaling system.Conclusions The above mentioned mechanism can partly explain the potential therapeutic benefit of atorvastatin in the treatment of atherosclerosis.