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.