Objective :To investigate the role of acyl-CoA :cholesterol acyltransferase 1 (ACAT1 ) in THP-1-derived foam cell formation induced by visfatin ,and to discuss the mechanism of visfatin-induced foam cell formation .Methods :THP-1 monocytes were induced into macrophages by 160 nmol/L phorbol myristate acetate (PMA )for 48 h,then the macrophages were added with visfatin (1× 10-7 mol/L1×10s mol/L )for 0 to 48 h .Lipid droplets in cytoplasm were observed by Oil red 0 staining .The contents of intracellular total cholesterol (TC ) and free cholesterol (FC ) were detected by enzyme fluorescence analysis .The contents of cholesterol ester (CE ) were calculated by the difference between TC and FC .The expressions of ACAT1 mRNA and protein were determined by RT-PCR and Westem blot respectively .Results :The lipid droplets of THPO-1-derived macrophages were increased by visfatin and the ratios of CE to TC were much higher than 50％ .The expression of' ACAT1 mRNA and protein was up-regulated by visfatin in both concentration-and time-dependent manner( P＜O .05 ) .Conclusion :The up-regulation of ACAT1 expression is involved in THP-1-derived foam cell formation induced by visfatin .This may provide a new evi dence for visfatin inducing atherosclerosis .%目的:观察酰基辅酶A:胆固醇酰基转移酶1 (ACAT1) 在内脂素(visfatin) 诱导THP-1源性泡沫细胞形成中的作用,以初步探讨visfatin诱导泡沫细胞形成的分子机制.方法:THP-1单核细胞诱导分化为巨噬细胞,予不同浓度的visfatin (1×10-7～1× 10-5 mol/L)分别作用0～48小时,运用油红O染色观察细胞浆脂滴变化,酶荧光法检测细胞内总胆固醇(TC)和游离胆固醇(FC)含量,TC与FC之差为胆固醇酯(CE)含量.分别运用RT-PCR和Western blot检测ACAT1 mRNA和蛋白表达.结果:与对照组比较,visfatin 干预组细胞浆脂滴明显增多,CE与TC的比值明显增加(>50%).visfatin呈浓度和时间依赖性地上调ACAT1 mRNA和蛋白表达(P＜0.05).结论:ACAT1表达上调是visfatin诱导THP-1源性泡沫细胞形成的机制之一,这可能为visfatin致动脉粥样硬化发病机制的研究提供一个新的理论依据.
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