过氧化体增殖物激活型受体γ配体抑制巨噬—泡沫细胞炎性介质和基质金属蛋白酶2的分泌  

Inhibitory Effect of Peroxisome Proliferator Activated Receptor γ Ligands on Secretion of Inflammatory Cytokine and Matrix Metalloproteinase in Macrophages and Foam Cell

作　　者：张俊峰[1] 葛恒[1] 王长谦[1] 邵琴[1] 

机构地区：[1]上海交通大学医学院附属仁济医院心内科,上海市200001

出　　处：《中国动脉硬化杂志》2006年第4期281-285,共5页Chinese Journal of Arteriosclerosis

基　　金：国家自然科学基金资助项目(30070869)

摘　　要：目的在证实泡沫细胞有过氧化体增殖物激活型受体γ表达的基础上,探讨其配体对巨噬细胞、泡沫细胞炎性介质和基质金属蛋白酶分泌的影响。方法体外诱导THP-1单核细胞分化为巨噬细胞,给予氧化型低密度脂蛋白进一步诱导其转变为泡沫细胞,应用逆转录聚合酶链反应检测过氧化体增殖物激活型受体γmRNA表达;过氧化体增殖物激活型受体γ配体吡格列酮干预后用Western blot检测巨噬细胞CD40蛋白的表达;用酶联免疫吸附测定法测定泡沫细胞培养上清液中白细胞介素6、肿瘤坏死因子α、基质金属蛋白酶2和9的浓度,Gelatin Zymog-raphy测定基质金属蛋白酶活性。结果巨噬细胞转化为泡沫细胞后其过氧化体增殖物激活型受体γ基因表达无显著变化。吡格列酮可显著抑制巨噬细胞CD40的表达,呈剂量依赖性;显著抑制泡沫细胞白细胞介素6、肿瘤坏死因子α和基质金属蛋白酶9的分泌(P<0.05),抑制基质金属蛋白酶9的活性,对基质金属蛋白酶2的分泌和活性无影响。结论巨噬细胞、泡沫细胞中过氧化体增殖物激活型受体γ基因表达无变化。过氧化体增殖物激活型受体γ配体从多个环节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,对防治动脉粥样硬化有利。Aim To investigate the effect of peroxisome proliferator-activated receptor γ （ PPARγ） ligands on inflammatory cytokine and matrix metalloproteinase （MMP） secretion by macrophages and foam ceil. Methods THP-1 monocytes were differentiated to macrophages in vitro by addition of PMA, and then induced into foam ceil by oxidizedd low density lipoprotein （ox-LDL）. Semi-quantitative reverse transcription polymerase chain reaction（RT-PCR） was performed to detect the expression of PPARγ. Macrophage CD40 protein expression was detected by Weslem blot. Interleukin 6 （IL-6 ）, tumor necrosis factor α （TNF-α） and MMP-9 secretion in foam cell culture medium was measured by enzyme-linked immunosorbent assay （ELISA）. MMP-9 activities were determined by gelatin zymography. Results Macrophages expressed PPARγ and treatment with ox-LDL did not affect the expression. PPARγ ligand pioglitazone greatly inhibited macrophage expression of CD40 in a dose-dependent manner. Moreover, pioglitazone significantly inhibited the secretion of ID6, TNF-α and MMP-9 by foam cell as well as the activity of MMP-9 （ P〈0.05 ）, although it had no effect on MMP-2 secretion or activity. Conclusions peroxisome proliferator-activated receptor γ ligands significantly inhibited the secretion of several inflammatory molecules by macrophages/foam cell which were closely related to atherosclerotic （As） plaque development and plaque instability. Thus, PPARγ ligands may have potential advantages in As therapy.

关 键 词：内科学 过氧化体增殖物激活型受体抗炎活性 巨噬-泡沫细胞 酶联免疫吸附试验 炎性介质 基质金属蛋白酶 动脉粥样硬化 

分 类 号：R543[医药卫生—心血管疾病]