Celebrex对VEGF诱导的内皮细胞迁移的影响及其机制  

Mechanism and Effect of Celebrex on the Migration Ability of ECV 304 Cells

作　　者：张懿敏[1] 韩国鸽[1] 范彪[2] 李琪[1] 李华[2] 魏蕾[2] 

机构地区：[1]武汉大学人民医院/武汉大学第一临床学院,湖北武汉430060 [2]武汉大学医学院病理生理学教研室

出　　处：《武汉大学学报（医学版）》2007年第4期434-437,455,共5页Medical Journal of Wuhan University

基　　金：武汉大学大学生科学研究基金项目（编号：20060358）

摘　　要：目的:观察选择性环氧化酶-2(COX-2)抑制剂celebrex对血管内皮生长因子(VEGF)诱导的内皮细胞细胞迁移能力的影响及其与细胞内MMP-9表达的关系。方法:体外培养内皮细胞系ECV304,将细胞分为4组:①空白对照组(ECV304);②VEGF组(ECV304+VEGF);③celebrex+VEGF组(ECV304+VEGF+cele-brex);④celebrex组(ECV304+celebrex)。观察:①用损伤修复实验观察不同浓度celebrex对ECV304细胞迁移能力影响及对VEGF诱导下ECV304细胞迁移速度影响;②用半定量RT-PCR法检测VEGF及celebrex对ECV304细胞MMP-9 mRNA表达的影响。结果:ECV304细胞的迁移速度随VEGF浓度(0.02,0.2,2μmol/L)的增加呈降低趋势;celebrex+VEGF组(2μmol/L celebrex+5μg/L VEGF)迁移速度为(3.55±0.02)μm/h与VEGF组(5μg/L VEGF)迁移速度(7.66±0.02)μm/h比较,两者有显著差异(P<0.01);celebrex+VEGF组(2μmol/L celebrex+5μg/L VEGF)的MMP-9表达量明显低于VEGF组(5μg/L VEGF)。结论:celebrex能抑制VEGF诱导的ECV304细胞迁移,并使COX-2下游的MMP-9表达量显著下调,这是可能的机制之一。Objective. To investigate the mechanism and effect of selective COX-2 inhibitor celebrex on the migration ability of ECV304 cells induced by VEGF and the relationship between celebrex and the expression of MMP-9. Methods： Cultured human ECV304 cells were divided into control group （ECV304）, VEGF group （ ECV304 ＋ VEGF）, elebrex ＋ VEGF group （ ECV304 ＋ VEGF ＋ celebrex） and celebrex group （ECV304＋celebrex）. The wound healing assay was used to observe the effect of celebrex of different concentration on the migration ability of ECV304 cells and the effect of celebrex on the migration velocity of ECV304 cells induced by VEGF. The MMP-9 mRNA expression of ECV304 cells treated by celebrex and VEGF was detected by RT-PCR. Results： The migration velocity of ECV304 cells decreased according to the increasing concentration of VEGF （0.02,0.2 and 2 μmol/L） ;the migration velocity of celebrex＋VEGF group （2 μmol/L celebrex ＋5 μg/L VEGF） was （3.55±0.02） μm/h and that of VEGF group （5 μg/L VEGF） was （7. 66±0.02）μm/h （P〈0.01）. The expression level of MMP-9 of celebrex＋VEGF group （2 μmol/L celebrex ＋5 μg/L VEGF） was lower than that of VEGF group （5 μg/L VEGF） significantly. Conclusion： Celebrex inhibits VEGF-induced ECV304 cells＇ migration. One of the possible mechanisms is that celebrex inhibits the expression of MMP-9 which located on the down-stream of COX-2 significantly.

关 键 词：血管内皮生长因子 塞来昔布 内皮细胞 迁移 

分 类 号：R363.21[医药卫生—病理学]