本文旨在观察过氧化物酶体增殖物激活受体γ(peroxisome proliferator-activated receptorγ,PPARγ)信号转导通路在内脂素(visfatin)调控人单核细胞株THP-1源性巨噬细胞ATP结合盒转运蛋白A1(ATP binding cassette transporter A1,ABCA1)和酰基辅酶A:胆固醇酰基转移酶1(acyl-CoA:cholesterol acyltransferase1,ACAT1)表达中的作用,探讨内脂素诱导泡沫细胞形成的机制和途径。THP-1单核细胞经佛波酯诱导分化为巨噬细胞,随机分组,给予不同浓度的内脂素和PPARγ激动剂罗格列酮(rosiglitazone)进行干预,分别运用RT-PCR和Western blot法检测各组细胞PPARγ、ABCA1及ACAT1 mRNA和蛋白表达,酶荧光学法检测细胞内总胆固醇(total cholesterol,TC)和游离胆固醇(free cholesterol,FC)含量,TC与FC之差为胆固醇酯(cholesterol ester,CE)含量。结果显示,内脂素呈浓度依赖性增加THP-1源性巨噬细胞内FC和CE含量,下调巨噬细胞PPARγ mRNA和蛋白的表达,同时下调其下游的靶基因ABCA1 mRNA和蛋白的表达,上调ACAT1 mRNA和蛋白的表达;而罗格列酮呈浓度依赖性地抑制内脂素所诱导的上述效应。上述结果提示,内脂素可能通过PPARγ信号转导通路下调ABCA1表达,上调ACAT1表达,使细胞内FC流出减少,CE合成增加,从而诱导泡沫细胞的形成。这为研究内脂素致动脉粥样硬化的机制提供了新的理论依据。 This study aimed to observe the effect of peroxisome proliferator-activated receptorγ (PPARγ) signal transduction pathway on the regulation of THP-1-derived macrophages ATP by visfatin To investigate the mechanism of visfatin-induced foam cell formation by the role of ABCA1 and acyl-CoA: ACAT1 expression way. THP-1 monocytes were induced to differentiate into macrophages by phorbol ester and randomly divided into groups. The cells were treated with different concentrations of visfatin and rosiglitazone, a PPARγ agonist. RT-PCR and Western blot The expression of PPARγ, ABCA1 and ACAT1 mRNA and protein were detected by enzyme-linked immunosorbent assay. The contents of total cholesterol (TC) and free cholesterol (FC) were measured by enzyme-linked immunosorbent assay. The difference between TC and FC was cholesterol ester ester, CE) content. The results showed that visfatin increased the content of FC and CE in THP-1-derived macrophages in a concentration-dependent manner, down-regulated the mRNA and protein expression of PPARγ in macrophages and down-regulated the expression of ABCA1 mRNA and protein, Up-regulated the expression of ACAT1 mRNA and protein, whereas rosiglitazone inhibited visfatin-induced above effects in a concentration-dependent manner. These results suggest that visfatin may down-regulate the expression of ABCA1 and up-regulate the expression of ACAT1 through the PPARγ signaling pathway, resulting in the decrease of intracellular FC efflux and the increase of CE synthesis, thus inducing the formation of foam cells. This provides a new theoretical basis for studying the mechanism of visfatin-induced atherosclerosis.