PPARs配体对巨噬细胞、泡沫细胞细胞外基质金属蛋白酶诱导因子表达的影响  

Effect of PPAR ligands on extracellular matrix metalloproteinase inducer expression in macrophages and foam cells

作　　者：张俊峰[1] 葛恒[1] 郭炳诗[2] 王长谦[1] 

机构地区：[1]上海第二医科大学附属仁济医院心内科 [2]上海第二医科大学/中科院上海生命科学院健康科学中心,上海200001

出　　处：《中国病理生理杂志》2006年第8期1519-1523,共5页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.30070869)

摘　　要：目的:观察PPARα、γ配体对巨噬细胞、泡沫细胞细胞外基质金属蛋白酶诱导因子(EMMPR IN)表达的影响。方法:体外诱导THP-1单核细胞转化为巨噬细胞、泡沫细胞,分别加入PPARα配体氯贝特(c lofibrate)、PPARγ配体吡格列酮(p ioglitazone)共同培养,应用Real-tim e RT-PCR和W estern b lotting测定巨噬细胞、泡沫细胞中EMMPR IN基因和蛋白表达,ELISA测定细胞培养上清液MMP-9浓度,Zymgraphy法测定MMP-9活性。结果:氯贝特和吡格列酮均能显著抑制巨噬细胞和泡沫细胞EMMPR IN的表达,此抑制作用与PPARα、γ配体抑制MMP-9分泌及活性的趋势一致。结论:PPARα、γ配体均可抑制巨噬细胞、泡沫细胞EMMPR IN的表达,下调EMMPR IN可能是PPAR s配体抑制粥样斑块局部MMPs产生的机制之一。AIM： To investigate the role of PPAR α or γ ligands in regulating the expression of extracellular matrix metalloproteinase inducer （EMMPRIN）. METHODS： THP - 1 monocytes were induced into macrophages and foam cells in vitro then interfered with clofibrate and pioglitazone. The cells and supematant were colleαed after 24 h, respeαively. EMMPRIN gene and its protein were assessed by real - time PCR and Western blotting in different interferences. The concentration of matrix metalloproteinases （ MMP -9 ） was measured with ELISA method and the aαivity of MMP -9 was detected with gelatin zymography. RESULTS： Two known PPAR α or γ ligands, colfibrate and pioglitzaone, were found, both of which inhibited EMMPRIN expression in macrophages and foam cells. The inhibition was correspondent to the secretion and aαivity of MMP-9 simultaneously. CONCLUSION： Both PPAR α and γ ligands inhibit EMMPRIN expression, which may account for their effeα on inhibition of MMPs.

关 键 词：过氧化物酶体增殖物激活受体 细胞外基质金属蛋白酶诱导因子 基质金属蛋白酶 动脉硬化 

分 类 号：R363[医药卫生—病理学]