PPARα配体对泡沫细胞炎性介质分泌的影响

Effect of PPARα ligands on secretion of inflammatory cytokines in foam cells

目的在证实泡沫细胞有过氧化物酶体增殖物激活受体α(PPARα)表达的基础上,探讨其配体对泡沫细胞炎性介质分泌的影响。方法体外诱导THP-1单核细胞分化为巨噬细胞,给予oxLDL进一步诱导其转变为泡沫细胞,应用RT-PCR检测PPARα基因表达;PPARα配体氯贝丁酯(50μmol/L)干预后用ELISA法测定泡沫细胞培养上清液中IL-6、TNF-α、MMP-2、MMP-9浓度,Gelatin Zymography测定MMPs活性。结果巨噬细胞转化为泡沫细胞后其PPARα基因表达无显著变化;氯贝丁酯可显著抑制泡沫细胞IL-6、TNF-α(P<0.05)、MMP-9(P<0.01)的分泌,抑制MMP-9的活性,对MMP-2的分泌和活性无影响。结论PPARα配体抑制致动脉粥样硬化炎性因子的分泌,减少基质金属蛋白酶的释放并抑制其活性,对防治粥样硬化有利。

AIM To investigate the effect of PPARα ligands on the inflammatory cytokine secretion by foam cells. METHODS THP-1 monocytes were differentiated to macrophages in vitro and then were induced into foam cells by culturing with oxLDL. Semi-quantitative RT-PCR was performed to detect the expression of PPARαgene. IL-6, TNF-α, MMP-2 and MMP-9 secretion into the foam cell culture medium were measured by ELISA. MMPs activities were determined by gelatin zymography. RESULTS Treatment of oxLDL did not affect macrophage expression of PPARα. Clofibrate, a PPARα ligand, significantly inhibited the secretion of IL-6, TNF-α （P 〈0.05 ） and MMP-9 （P 〈0.01 ） by foam cells as well as MMP-9 activity. MMP-2 secretion and activity were not affected. CONCLUSION PPARα ligand significantly inhibits foam cell secretion of several inflammatory molecules known to be closely associated with atherosclerotic plaque development and plaque instability. Therefore PPARα ligands may have some potential effects in the treatment of atherosclerosis.