【摘要】 目的观察NF-κB抑制剂咖啡酸苯乙酯(CAPE)对溶血磷脂酸(LPA)诱导人单核细胞(THP-1)基质金属蛋白酶9(MMP-9)表达和活性及NF-κB p65表达的影响。方法选用THP-1培养后,分对照组(不加LPA),加0.1、0.5、1、5和10μmol/L LPA依次为1组、2组、3组、4组和5组,刺激THP-1细胞4 h;另选CAPE 20 mg/L预处理1 h,再LPA 1μmol/L处理4 h后为CAPE组,ELISA法测定MMP-9含量,酶谱法检测MMP-9活性,蛋白印迹法检测核蛋白NF-κB p65表达变化。结果与对照组和1组、2组、4组、5组比较,3组MMP-9分泌和活性以及NF-κB p65均显著增加,差异有统计学意义(P<0.01);与3组比较,CAPE组明显抑制上述指标(P<0.01)。结论 LPA可能通过激活NF-κB,促进MMP-9表达,并增强其活性,而CAPE抑制MMP-9表达。更多还原

【Abstract】 Objective To study the effect of nuclear factor-kappaB(NF-κB) inhibitor caffeic acid phenethyl ester(CAPE) on the lysophosphatidic acid ( LPA)-induced expression and activity of matrix metalloproteinase-9(MMP-9)and the activity of NF-κB p65 protein in inTHP-1cell line and to investigate the role of NF-κB,MMP-9 in the atherosclerosis caused by LPA.Methods Human THP-1 cells were stimulated with LPA at different concentrations(0—10μmol/L)for 4 h,or preincubated with CAPE for 1 h and then stimulated with LPA at 1 μmol/L for 4 h.The expression and activity of MMP-9 was measured by enzyme-linked immunosorbent assay or gelatin zymography. The activity of NF-κB p65 was detected by Western blot.Results LPA upregulated the gene expression and activity of MMP-9,activated the NF-κB p65 in a dose-dependent manner,the peak point occurred at 1μmol/L LPA and decreased at higher LPA concentrations (P < 0.01),which can be significantly depressed by CAPE (P< 0.01).Conclusion LPA can increase the expression and activity of MMP-9 through the activation of NF-κB pathway in THP-1 cells,which may be depressed by CAPE.更多还原