铁离子螯合剂去铁胺对巨噬细胞、泡沫细胞细胞外基质金属蛋白酶诱导因子表达的影响  

Iron chelator desferrioxamine enhances EMMPRIN expression in THP-1-derived macrophages and foam cells

作　　者：范虞琪[1] 何奔[1] 王彬尧[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200001

出　　处：《心脏杂志》2009年第5期601-605,共5页Chinese Heart Journal

基　　金：国家自然科学基金项目资助(30670880);上海市科委基础研究项目资助(08XD1402600)

摘　　要：目的:观察铁负荷过低对巨噬细胞、泡沫细胞细胞外基质金属蛋白酶诱导因子(EMMPRIN)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。实验细胞分为3组:对照组(正常巨噬细胞、泡沫细胞)、铁离子螯合剂去铁胺(DFO)刺激组、柠檬酸铁和DFO共刺激组。应用RT-PCR和Western blot测定巨噬细胞、泡沫细胞中EMMPRIN基因和蛋白的表达。用Western blot测定MMP-9蛋白的表达。用明胶酶谱法测定MMP-9的活性。结果:DFO刺激组中EMMPRIN基因及蛋白的水平、MMP-9蛋白表达的水平及活性均明显高于对照组(P<0.05,P<0.01)。柠檬酸铁逆转了DFO对EMMPRIN表达的上调作用。结论:铁负荷过低可增加巨噬细胞及泡沫细胞中炎症因子的表达及活性,可能会促进心血管事件的发生。AIM： To observe the effect of iron depletion on extracellular matrix metalloproteinase inducer （EMMPRIN） expression in macrophages and foam cells. METHODS： THP-1 monocytes were induced to macrophages and foam cells. Cells were then divided into three groups ： 1 ） normal macrophages/foam cells as control, 2 ） cells treated with different concentrations of desferrioxamine （ DFO ）, 3 ） cells co-treated with ferric citrates and DFO. EMMPRIN mRNA and protein expression were assayed by RT-PCR and Western blot. MMP-9 expression was assayed by Western blot and its invasive activity was assayed by gel zymography. RESULTS： DFO significantly enhanced EMMPRIN mRNA and protein expression in macrophages and foam cells and upregulated MMP-9 expression and invasive activity （ P 〈 0. 05, P 〈 0. 01 ） CONCLUSION ： Iron depletion therapy enhances production of inflammatory factors in macrophages and foam cells, which may cause deadly cardiovascular events.

关 键 词：去铁胺 细胞外基质金属蛋白酶诱导因子 基质金属蛋白酶 动脉粥样硬化 

分 类 号：Q559[生物学—生物化学]