4-羟基苯乙酸对M1型巨噬细胞极化及巨噬细胞泡沫化的影响

Effect of 4-Hydroxyphenylacetic acid on M1 macrophage polarization and the formation of macrophage-derived foam cells

以多酚肠道菌群代谢物4-羟基苯乙酸(4-hydroxyphenylacetic acid,4-HPAA)为试验对象,研究其对M1型巨噬细胞极化及巨噬—泡沫细胞形成的影响。结果表明,4-HPAA能降低巨噬细胞M1极化标志基因TNF-α、IL-6和IL-1β的mRNA表达及分泌水平,抑制RAW264.7巨噬细胞向促炎的M1型巨噬细胞极化;油红O染色结果显示4-HPAA可显著降低ox-LDL诱导的巨噬细胞中脂滴蓄积,并显著降低胆固醇酯的含量(P<0.05)。RT-PCR结果显示4-HPAA可显著上调ox-LDL诱导的泡沫细胞三磷酸腺苷结合盒转运蛋白G1(ABCG1),下调白细胞分化抗原36(CD36)基因的表达水平(P<0.05)。说明4-HPAA能抑制巨噬细胞M1型极化,同时能抑制巨噬细胞泡沫化,表明多酚肠道菌群代谢物4-HPAA可能在其改善动脉粥样硬化的过程中发挥重要作用。

The aim of the present study is to investigate the potential anti-atherogenic effect of 4-hydroxyphenylacetic acid(4-HPAA),a major microbiota-derived metabolite of polyphenols,on macrophagepolarization and the formation of macrophage derived-foam cells as well as the underlying molecular mechanisms.4-HPAA treatment could-significantly decrease the secretion and mRNA levels of TNFα,IL-6 and IL-1βof M1 macrophages induced by lipopolysaccharide(LPS)and interferon-γ(IFN-γ),indicating its ability to inhibit the polarization of macrophage cell into pro-inflammatory M1-typemacrophage.The results of oil red O staining revealedthat 4-HPAA significantly inhibited theaccumulation of lipid droplets in a dose-dependent manner compared with the model cells.In addition,4-HPAA significantly decreased the content of intracellular cholesterol esters.RT-PCR results showed that compared with the model group,4-HPAA significantly up-regulated ABCG1 and down-regulated CD36 gene expression level(P<0.05),which was associated with macrophage cholesterol efflux.In conclusion,the results showed that the potential role of 4-HPAA in preventing M1 macrophage polarization and foam cell formation,which may play an important role in the anti-atherogenic effect of polyphenols.