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

中国临床药理学与治疗学 ›› 2007, Vol. 12 ›› Issue (1): 52-56.

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

李健哲, 陈颇静, 蔡志春, 黎敏, 王晨静, 吴建华, 方云祥

中南大学药学院药理教研室, 长沙 410078, 湖南

收稿日期:2006-09-06 修回日期:2006-10-23 出版日期:2007-01-26 发布日期:2020-10-26
通讯作者: 方云祥, 男, 教授, 博士生导师, 研究方向:心脑血管药理学。Tel:0731-2355082 　E-mail: yunxiangf@yahoo.com.cn.
作者简介:李健哲, 男, 硕士, 研究方向:心脑血管药理学。Tel:13975105746 E-mail:lijianzhe20035@126.com

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

LI Jian-zhe, CHEN Po-jing, CAI Zhi-chun, LIMin, WANG Chen-jing, WU Jian-hua, FANG Yun-xiang

Department of Pharmacology, Xiangya School of Medicine, Central South University, Changsha 410078, Hunan, China

Received:2006-09-06 Revised:2006-10-23 Online:2007-01-26 Published:2020-10-26

摘要/Abstract

摘要： 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) 5 mg/L作用0 、12 、24 、48 h, 观察LPC 对ICAM 和MMP-9 表达的影响。不同浓度(10-7 ~ 10-5 mol/L) 的氟伐他汀预先孵育20 min, 然后加入LPC(5 mg/L) 作用24 h, 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 (vaseular cell adhesionmolecule-1, VCAM-1) 蛋白和用RT-PCR 检测MMP-9 mRNA 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。

关键词: 氟伐他汀, 溶血磷脂酰胆碱, 人脐静脉内皮细胞, 动脉粥样硬化, 细胞间粘附分子-1, 血管细胞粘附分子-1, 核因子-кBp65, 基质金属蛋白酶-9

Abstract: AIM: To observe the effect of fluvastatin on the expression of adhesion molecule and matrix metalloproteinase-9 (MMP-9) induced by lysophosphatidylcholine (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 immunohistochemical 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.

Key words: fluvastatin, lysophosphatidylcholine, human umbilical vein endothelial cell, atherosclerosis, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, nuclear factor-кBp65, matrix metalloproteinase-9

中图分类号:

R965.2
R966

李健哲, 陈颇静, 蔡志春, 黎敏, 王晨静, 吴建华, 方云祥. 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[J]. 中国临床药理学与治疗学, 2007, 12(1): 52-56.

LI Jian-zhe, CHEN Po-jing, CAI Zhi-chun, LIMin, WANG Chen-jing, WU Jian-hua, FANG Yun-xiang. Effect of fluvastatin on expression of adhesion molecule and matrix metalloprpteinase-9 induced by lysophosphatidylcholine in human umbilical vein endothelial cell[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2007, 12(1): 52-56.

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