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

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。

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

Objective To study the effect of atorvastatin on gene expression profile in EA.hy926 cells and its molecular mechanism.Methods EA.hy926cells were divided into experimental group and control group.Experimental group was treated with 10μmol/L atorvastatin for 24h. Effect of atorvastatin on gene expression profile in EA.hy926cells was detected by Affymetrix HG-U133plus 2.0oligonucleotide 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 649genes with their differential expression>2were detected after treated with atorvastatin.The expression level of 295genes was higher and that of 354genes 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.