尿石素A对巨噬细胞极化及巨噬-泡沫细胞形成的作用

Effect of Urolithin A on Macrophage Polarization and the Formation of Macrophage-Derived Foam Cells

旨在探究尿石素A对巨噬细胞极化及对巨噬-泡沫细胞形成的影响及相关的分子机制。结果发现,尿石素A通过调控不同标志基因的表达,不仅能够抑制RAW264.7小鼠巨噬细胞向促炎的M1型巨噬细胞极化,还能促进自然状态巨噬细胞向M2型巨噬细胞极化;油红O染色发现尿石素A能够显著抑制巨噬-泡沫细胞形成,实时荧光定量聚合酶链式反应检测说明尿石素A能够抑制胆固醇合成基因羟甲基戊二酸单酰辅酶A还原酶和脂肪酸合成酶基因的转录;此外,尿石素A显著上调三磷酸腺苷结合盒转运蛋白A1和G1基因的表达,该两个基因表达与促进了胆固醇的排出相关。本研究证明了尿石素A对巨噬细胞极化具有调控作用,同时尿石素A能够抑制巨噬-泡沫细胞形成和胆固醇合成。这些结果揭示了尿石素A具有潜在的抗动脉粥样硬化的作用,为之后深入研究提供了理论参考。

This research was designed to investigate the potential anti-atherogenic effect of urolithin A on macrophagepolarization and the formation of macrophage derived-foam cells as well as the underlying molecular mechanisms.It wasfound that urolithin A could mediate the mRNA expression of different marker genes in M1-type and natural macrophages,indicating its ability to inhibit the polarization of macrophage cell line(RAW264.7)into pro-inflammatory M1-typemacrophage and to promote the polarization of macrophage cells into M2type.The results of oil red O staining revealedthat urolithin A inhibited the formation of foam cells derived from macrophages.Real time PCR showed that urolithin Aalso markedly decreased the expression of3-hydroxy-3-methylglutaryl coenzyme A reductase and fatty acid synthase at thetranscriptional level.Besides,urolithin A was capable of up-regulating the mRNA expression of the ATP-binding cassettetransporters A1and G1,which was positively associated with macrophage cholesterol efflux.In summary,the findingsconfirmed the essential role urolithin A plays in macrophage polarization,and further demonstrated the potential molecularmechanisms of urolithin A in preventing foam cell formation and cholesterol synthesis,which are of great significance ininvestigating and understanding the anti-atherogenic effect of urolithin A in the future.