目的研究泡沫细胞形成过程中肿瘤坏死因子-α(TNF-α)对乙酰辅酶A:胆固醇酰基转移酶1(ACAT1)基因的影响。方法体外培养人THP-1单核细胞系,由佛波酯作用使其分化为巨噬细胞,再由乙酰化低密度脂蛋白作用转变为泡沫细胞。TNF-α分别作用于上述三种细胞24h,用Western blot法检测ACAT1蛋白表达,RT-PCR法检测ACAT1 mRNA水平。结果在单核细胞分化为巨噬细胞及转变为泡沫细胞的过程中,ACAT1蛋白及mRNA均增加(P均〈0.05);TNF-α可上调三种细胞ACAT1蛋白表达及mRNA水平(P均〈0.05)。结论单核细胞分化为巨噬细胞及转变为泡沫细胞的过程中,ACAT1基因表达明显增加,TNF-α可明显促进ACAT1基因表达。
[ Objective] To study the effects of tumor necrosis factor-α(TNF-α) on the expression of the acyl coenzyme A: cholesteryl acyltransferase 1 (ACAT1) during the formation of foam cells. [ Methods] THP-1 human monocytic leukemia cells ( THP-1 ) were cultured. The differentiation of THP-1 cells into macrophages (MPs) was induced by phorbol esters (PMA). The MPs were incubated with acyl-low density lipoprotein (Ac-LDL) to generate foam cells (FCs). TNF-α(60 ng/mL) was added in those three kinds of cells and incubated for 24 hours. The levels of ACAT1 protein and mRNA were detected by western blotting and RT-PCR. [ Results ] The ACAT1 protein and ACAT1 mRNA were significantly increased during the differentiation of monocytes into macrophages and the formation of foam cells ( P 〈 0.05 ). TNF-α stimulated the expression of ACAT1 protein and ACAT1 mRNA (P 〈 0.05 ). [ Conclusion ] The ACAT1 gene expression is up-regulated during the differentiation of monocytes into macrophages and the formation of foam cells. TNF-α significantly increases the expression of ACAT1 gene.