血管紧张素Ⅱ对巨噬细胞和泡沫细胞ACAT-1及PPAR-γ表达的影响

Effects of angiotensin Ⅱ on expression of acyl-coenzyme A: cholesterol acyltransferase-1 and peroxisome proliferator-activated receptor-γ in macrophages and foam cells

目的:观察血管紧张素Ⅱ(AngⅡ)对巨噬细胞和泡沫细胞过氧化体增殖物激活型受体γ(PPAR-γ)和酰基辅酶A:胆固醇酰基转移酶-1(ACAT-1)表达的影响。方法:将单核细胞株THP-1与160 nmol/L佛波酯(PMA)孵育48 h,使之分化为巨噬细胞,继以100 mg/L氧化型低密度脂蛋白(ox-LDL)诱导巨噬细胞分化为泡沫细胞。将巨噬细胞和泡沫细胞用1×10-6 mol/L AngⅡ孵育48 h。运用RT-PCR和Western blot分别检测PPAR-γmRNA、ACAT-1mRNA及其蛋白的表达水平。结果:单核细胞在分化为巨噬细胞和泡沫细胞的过程中,PPAR-γ的表达明显降低(P<0.05),ACAT-1的表达显著增强(P<0.05);经AngⅡ干预后,巨噬细胞和泡沫细胞PPAR-γ的表达进一步降低(P<0.05,P<0.05),而ACAT-1的表达更加增强(P<0.05,P<0.05)。结论:AngⅡ不但可上调巨噬细胞和泡沫细胞中ACAT-1的表达,而且可抑制PPAR-γ的表达。

AIM： To investigate the effects of angiotensin II（Ang II） on expression of acyl-coenzyme A： cholesterol acyltransferase-1（ACAT-1） and peroxisome proliferator-activated receptor-γ（PPAR-γ） in macrophages and foam cells.METHODS： After human THP-1 cells were incubated with 160 nmol/L PMA for 48 h to differentiate into macrophages,the macrophages were cultured with 100 mg/L oxidized LDL for 24 h to differentiate into foam cells.Macrophages and foam cells were incubated with 1×10-6 mol/L Ang II for 48 h.ACAT-1 mRNA and PPAR-γ mRNA were detected by reverse transcription polymerase chain reaction（RT-PCR） and protein levels of ACAT-1 and PPAR-γ were measured by Western blot.RESULTS： ACAT-1 mRNA and protein levels were upregulated significantly（P〈0.05） during differentiation from monocytes into macrophages and differentiation from macrophages into foam cells,with the PPAR-γ mRNA and protein levels significantly downregulated（P〈0.05）.When treated with Ang II,the ACAT-1 mRNA and protein levels of macrophages and foam cells were up-regulated more significantly（P〈0.05,P〈0.05） and their PPAR-γ mRNA and protein levels were more significantly downregulated（P〈0.05,P〈0.05）.CONCULUSION： Ang II not only significantly promotes ACAT-1 expression but also inhibits PPAR-γ expression during the monocytes-macrophages differentiation.