厄贝沙坦调节EA.hy926细胞动脉粥样硬化相关炎症基因的表达水平  

Irbesartan regulates inflammatory gene expressions related to atherosclerosis in EA.hy926 cells

作　　者：马聪[1] 卢学春[2] 范利[1] 罗芸[3] 杨波[2] 高燕[1] 刘先锋[1] 

机构地区：[1]解放军总医院南楼临床部心血管内科,北京100853 [2]解放军总医院南楼临床部血液科,北京100853 [3]解放军总医院南楼临床部老年医学研究所细胞生物学研究室,北京100853

出　　处：《南方医科大学学报》2011年第11期1835-1839,共5页Journal of Southern Medical University

基　　金：国家科技部支撑计划(2009BAI86B04)~~

摘　　要：目的观察厄贝沙坦是否调节人脐静脉内皮细胞株EA.hy926动脉粥样硬化相关炎症基因表达谱的变化。方法人脐静脉内皮细胞株EA.hy926与厄贝沙坦(10-6 mol/L)共同孵育24 h,提取总RNA行基因表达谱分析。DAVID平台分析对照组和加药组之间疾病相关的差异基因,实时定量聚合酶链反应(RT-PCR)验证动脉硬化相关基因表达水平。Western blotting验证血管紧张素1型受体(AT1R)和血管紧张素2型受体(AT2R)蛋白水平的变化。结果基因芯片表达谱分析中,与对照组相比,共56条差异基因,其中39条基因表达水平上调,17条基因下调。疾病分类分析提示这些基因与冠状动脉粥样硬化、心肌梗死、结直肠癌等疾病相关。其中与动脉粥样硬化及心肌梗死相关的基因有8条,分别是MMP2、PTGS2、PECAM1、SELP、SELL、CYP1A1、MMRN1、HSPA1A。RT-PCR验证结果与芯片结果基本相符。Westren blotting提示厄贝沙坦组AT1R表达较对照组减低,AT2R表达增加。结论厄贝沙坦调节人脐静脉内皮细胞株EA.hy926动脉粥样硬化相关炎症因子的表达,这些因子能够增加动脉粥样硬化斑块的不稳定性,促炎因子表达的机制可能是AT2R的过表达。Objective To characterize if irbesartan regulates vascular inflammatory gene expression profiles related to atherosclerosis in EA.hy926 cells.Methods Human umbilical vein endothelial cell line EA.hy926 cultured in vitro was incubated with irbesartan（1×10-6 mol/L） for 24 h.The total RNA was extracted from the cells for gene expression profiling.The DAVID Gene Functional Classification Tool was used to analyze the disease-and function-related genes in the cells.Real-time quantitative polymerase chain reaction（RT-PCR） was used to verify the genes showing differential expression after irbesartan treatment.The protein levels of angiotensin II type 1 receptor（AT1R） and type 2 receptor（AT2R） were tested by Western blotting.Results Compared with the control cells,56 genes were found to show marked changes following irbesartan treatment,including 39 up-regulated and 17 down-regulated genes.Disease analysis suggested that these genes were related to such diseases as coronary atherosclerosis,myocardial infarction,and colorectal cancer.Eight genes,namely MMP2,PTGS2,PECAM1,SELP,SELL,CYP1A1,MMRN1,and HSPA1A,were involved in atherosclerosis and myocardial infarction.Verification by RT-PCR produced a result consistent with the gene array result.AT1R was down-regulated while AT2R up-regulated in irbesartan-treated cells.Conclusion Irbesartan regulates the inflammatory gene expressions related to atherosclerosis in EA.hy926 cells.These inflammatory factors may promote destabilization of atherosclerotic plaque possibly in relation to AT2R overexpression.

关 键 词：血管紧张素受体拮抗剂 厄贝沙坦 血管紧张素Ⅱ1型受体 血管紧张素II2型受体 炎症 动脉粥样硬化 

分 类 号：R543.5[医药卫生—心血管疾病]