阿托伐他汀钙对EA.hy926细胞全基因表达谱的影响及生物信息学分析  

Effect of atorvastatin on gene expression profile in EA.hy926 cells and its molecular mechanism

作　　者：高燕[1] 范利[2] 卢学春[2] 刘先锋 马聪[2] 罗芸[4] 赵霞[1] 裴晶[1] 

机构地区：[1]济南军区总医院干三科,250031 [2]解放军总医院南楼临床部 [3]解放军401医院干部病房三科 [4]解放军总医院老年病研究所细胞生物学研究室

出　　处：《中华老年心脑血管病杂志》2014年第2期133-138,共6页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

基　　金：国家科技支撑计划项目(2009BAI86B04)

摘　　要：目的探讨阿托伐他汀钙对体外培养人脐静脉内皮细胞EA.hy926细胞基因表达谱的影响及作用的分子机制。方法取EA.hy926细胞分实验组和对照组,实验组采用10μmol/L阿托伐他汀钙体外干预人脐静脉内皮细胞EA.hy926 24h,用Affymetrix HG-U133plus 2.0全基因组表达芯片检测阿托伐他汀钙对EA.hy926细胞基因表达谱的影响。并运用基因富集分析(GSEA)软件、DAVID基因功能聚类分析软件及Cmap数据库对芯片数据进行分析,对相关靶基因进行实时定量PCR验证。结果与对照组比较,实验组基因芯片分析筛选出差异表达倍数>2倍的基因649个,其中上调基因295个,下调基因354个。经DAVID及GSEA基因富集分析显示,阿托伐他汀钙广泛下调了细胞周期调控相关基因,上调了Kruppel样转录因子等血管保护基因,Cmap数据库分析显示,阿托伐他汀钙与组蛋白去乙酰化酶抑制剂及白藜芦醇呈正相关的联强度高。结论阿托伐他汀钙从多角度发挥抗动脉粥样硬化作用,作用机制可能与组蛋白去乙酰化酶抑制剂及白藜芦醇相似。Objective To study the effect of atorvastatin on gene expression profile in EA.by926 cells and its molecular mechanism.Methods EA.hy926 cells were divided into experimental group and control group.Experimental group was treated with 10μmol/L atorvastatin for 24 h.Effect of atorvastatin on gene expression profile in EA.hy926 cells was detected by Affymetrix HG-U133 plus 2.0 oligonucleotide microarray.Gene expression data were analyzed by GSEA and DAVID analysis respectively.The related target genes were validated by RT-PCR.Results A total of 649 genes with their differential expression ＞2 were detected after treated with atorvastatin.The expression level of 295 genes was higher and that of 354 genes was lower in experimental group than in control group.GSEA and DAVID analysis showed that atorvastatin down-regulated the expression of cell cycle-modulated genes and up-regulated the expression of blood vessel protective genes such as Kruppel-like factor.cMap analysis revealed that atorvastatin was closely related HDAC inhibitors and resveratrol.Conclusion Atorvastatin can prevent atherosclerosis as HDAC inhibitors and resveratrol.

关 键 词：羟甲基戊二酰基COA还原酶抑制剂 降血脂药 内皮细胞 基因表达 计算生物学 

分 类 号：R96[医药卫生—药理学]