摘要
目的基于生物信息学途径探讨阿托伐他汀钙与其他药物的相互作用。方法人脐静脉内皮细胞株EA．hy926分为阿托伐他汀钙（AT）组和二甲基亚砜（DMSO）组，分别加入1×10^-5mol／L阿托伐他汀钙和等体积DMSO培养24h，提取总RNA进行基因表达谱分析，SAM软件分析AT组和DMSO组差异表达倍数在2倍以上的基因。采用基因集富集分析（GSEA）方法对阿托伐他汀钙处理后的内皮细胞基因表达谱进行通路富集分析。使用Connectivity Map（Cmap）筛选与阿托伐他汀钙有相互作用的药物。结果基因芯片表达谱分析共获得AT组与DMSO组比较差异表达2倍以上的基因649个，其中上调基因295个、下调基因354个。使用GSEA进行通路富集分析显示，与DMSO组比较，AT组13条通路中的基因表达上调、113条通路中的基因表达下调。Cmap分析筛选出MS-275、trichostatinA、vorinostat等组蛋白去乙酰化酶抑制剂、白藜芦醇、吩噻嗪类衍生物等药物的正性富集分数较高。结论基于生物信息学途径研究药物相互作用切实可行。阿托伐他汀钙与组蛋白去乙酰化酶抑制剂、白藜芦醇及吩噻嗪类衍生物有协同作用。
Objective To explore the drug interactions between atorvastatin calcium and other drugs based on bioinformatics. Methods The human umbilical vein endothelial cell line EA.hy926 cultured in vitro was assigned to be incubated for 24 h with 1×10-5 mol/L atorvastatin calcium （AT group） or with equal volume of dimethyl sulfoxide （DMSO group）. Total RNA from these cells was extracted and performed for gene expression profiling. The SAM microarray analysis software was used to analyze the genes with two- fold or higher differenced expression between two groups. Gene set enrichment analysis （GSEA） was used for pathway enrichment analysis of the gene expression profiles in endothelial cells treated with atorvastatin calcium. Connectivity Map （Cmap） was used to screen the drugs interactive with atorvastatin calcium. Results Microarry gene expression profiling showed that there were 649 genes with 2- fold or higher differenced expression between AT group and DMSO group, including 295 up- regulated and 354 down- regulated. GSEA analysis showed up-regulated gene expression in 13 pathways, and down-regulated gene expression in 113 pathways of the AT group compared with DMSO group. In Cmap analysis, the profiles of the several histone deacetylases （HDAC） inhibitor （MS-275, trichostatin A, vorinostat, etc.）, resveratrol and phenothiazines derivatives were found to have higher scores of enrichment. Conclusions The study of drug interactions based on the bioinformatics is feasible. Atorvastatin calcium has a synergistic effect with HDAC inhibitor, resveratrol and phenothiazine derivatives.
出处
《中华生物医学工程杂志》
CAS
2014年第5期357-361,共5页
Chinese Journal of Biomedical Engineering
基金
济南军区总医院2012年院长基金（20128005）
作者简介
通信作者：高燕，Email：gaoyantianyu74@163．com
