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目的观察溶血磷脂酸(Lysophosphatidie Acid,LPA)对人单核细胞株THP-1细胞基质金属蛋白酶-9(matrix metalloproteinases-9)表达及活性和NF-κB p65表达活性的影响,探讨MMP-9在LPA致动脉粥样硬化中的作用及机制。方法以不同浓度水平LPA(0~10μmol/L)刺激人THP-1细胞4h,RT-PCR法测定MMP-9mRNA表达,酶谱法检测MMP-9活性,westernblot检测核蛋白NF-κB p65表达变化。结果随着LPA剂量的增加,MMP-9表达及活性,核蛋白NF-κB p65表达逐渐增强,在LPA1μmol/L时达到最高点,然后逐渐减弱,LPA以剂量依赖的方式激活NF-κB,上调THP-1细胞MMP-9表达,增加MMP-9活性。结论LPA可能通过激活NF-κB,在转录水平促进THP-1细胞MMP-9mRNA表达,并增强其活性,促进粥样硬化发生和发展。
Objective To observe the effect of Lysophosphatidie Acid (LPA) on the expression and activity of matrix metalloproteinases-9 and the activity of NF-κB p65 in human monocytic THP-1 cells, The Role and Mechanism of LPA in Atherosclerosis. Methods Human THP-1 cells were stimulated with different concentrations of LPA (0-10μmol / L) for 4 hours. The expression of MMP-9 mRNA was detected by RT-PCR. The expression of NF-κB p65 was detected by western blot. . Results With the increase of LPA dose, the expression and activity of MMP-9 and the expression of nuclear NF-κB p65 protein gradually increased and reached the peak at 1μmol / L LPA, then gradually decreased. LPA activated NF-κB in a dose-dependent manner MMP-9 expression in THP-1 cells increases MMP-9 activity. Conclusion LPA may promote the expression of MMP-9 mRNA in THP-1 cells through activating NF-κB, enhance its activity and promote the occurrence and development of atherosclerosis.