氟伐他汀对溶血磷脂酰胆碱致内皮细胞粘附分子和基质金属蛋白酶-9表达的影响

Effect of fluvastatin on expression of adhesion molecule and matrix metalloprpteinase-9 induced by lysophosphatidylcholine in human umbilical vein endothelial cell

目的：观察氟伐他汀对内皮细胞粘附分子（intercellular adhesion molecule，ICMA）和基质金属蛋白酶-9（MMP-9）表达的影响，探讨氟伐他汀抗动脉粥样硬化（AS）的作用机制。方法：体外培养人脐静脉内皮细胞，待细胞生长到融合状态时加入溶血磷脂酰胆碱（lysophosphatidylcholine，LPC）5mg／L作用0、12、24、48h，观察LPC对ICAM和MMP-9表达的影响。不同浓度（10^-7 -10^-5mol／L）的氟伐他汀预先孵育20min，然后加入LPC（5nvdL）作用24h，用免疫细胞染色法检测核因子-κBp65（NF-κBp65）、ICAM-1、血管细胞粘附分子-1（vasettlar cell adhesion molecule-1。VCAM-1）蛋白和用RT-PCR检测MMP-9mRNA的表达水平。结果：LPC能明显增加ICAM-1、VCAM-1和MMP-9的表达，相关分析表明，NF-κBp65与ICAM-1、VCAM-1和MMP-9的表达呈直线相关关系。而预先应用不同浓度的氟伐他汀干预后，上述效应明显减弱，并且具有剂量依赖性。结论：LPC通过激活NF-κBp65而导致内皮细胞ICAM-1、VCAM-1和MMP-9的表达增强，而氟伐他汀对上述效应有抑制作用。

AIM： To observe the effect of fluvastatin on the expression of adhesion molecule and matrix metalloproteinase-9 （ MMP-9 ） induced by lysophosphatidyleholine （LPC）. METHODS： The HUVECs were incubated with LPC for 0, 12, 24 and 48 h to detect the expression of adhesion molecule and MMP-9. The HUVECs were incubated with fluvastatin of different concentration for 20 min before incubated with LPC for 24 h. The expression of NF-κBp65, intercellular adhesion molecule- 1 （ ICAM- 1 ） and （vaseular cell adhesion molecule- 1, （ VCAM-1 ） was detected by immunohistochemieal method, and the mRNA expression of MMP-9 was detected by RT-PCR. RESULTS： LPC could significantly induce the expression of ICAM-1, VCAM-1 and MMP-9.NF-κBp65 protein and ICAM-1 expressions were related in linear correlation, as well VCAM-1 and MMP-9 expresions. Fluvastatin could inhibit the aboving effects in a concentration-dependent manner. CONCLUSION： The NF-κB activation which is induced by LPC enhances the ICAM- 1, VCAM- 1 and MMP-9 expressions, while fluvastatin is able to inhibit these effects.