基因组水平筛选冠状动脉病变部位参与急性心肌梗死急性期的信号通路  

Screening of signal pathway in coronary artery lession involved in pathogenesis of acute myocardial infarction by gene level

作　　者：陈小琳[1] 钟诗龙[1,2,3] 张斌[1] 

机构地区：[1]广东省人民医院广东省医学科学院广东省心血管病研究所心内科,广州510080 [2]广东省人民医院广东省医学科学院广东省临床药理研究所,广州510080 [3]广东省人民医院广东省医学科学院医学研究中心,广州510080

出　　处：《岭南心血管病杂志》2011年第3期193-197,共5页South China Journal of Cardiovascular Diseases

基　　金：国家自然科学基金(项目编号:81072701);广东省自然科学基金(项目编号:10151008002000002)

摘　　要：目的利用基因芯片技术筛选冠状动脉病变部位参与急性心肌梗死急性期过程的信号通路,探讨急性冠脉综合征斑块破裂病变的发生机制。方法收集急性心肌梗死患者急性期和冠状动脉造影结果正常者的冠状动脉血,用人类基因组U133A寡核苷酸芯片筛选差异表达基因,然后采用DAVID功能注释生物信息学芯片分析系统对2倍差异表达基因进行基因富集分析,并用定量多聚酶连反应(RT-qPCR)验证化学因子信号通路部分筛选基因的表达。结果与冠状动脉造影正常者相比,急性心肌梗死患者在急性期的2倍上调基因有2897个,2倍下调基因有1974个。GO信号通路富集分析显示96个信号通路参与急性心肌梗死急性期过程(BenjaminiP>0.01)。KEGG信号通路富集分析显示6个信号通路参与急性心肌梗死急性期过程(BenjaminiP>0.01)。选择化学因子信号通路6个上下游基因进行验证,与芯片结果高度一致。其中CXCR1、CXCR2、Src、Raf和ERK1/2基因在急性期表达显著增高,与对照组比较,差异有统计学意义(P<0.001),而PI3K表达也有增高的趋势。结论在急性心肌梗死急性期过程中有许多信号通路参与,其中Chemokine信号通路与其发病机制密切相关。Objectives To identify signal pathways involved in pathogenesis of acute myocardial infarction（AMI） and unveil mechanism of AMI.Methods A genome wide expression scan of coronary blood from patients with AMI and without AMI by using Human Genome U133A Array screened the different expressive genes among the two groups.Real-time quantitative polymerase chain reaction （RT-qPCR） was used to validate the expression of genes in Chemokine signaling pathway.Results By comparative differential gene expression analysis among the two groups,the 2-fold upregulated genes of AMI patients during the acute phase were 2 897,and 2 fold down-regulated genes were 1 974.GO analysis revealed that enrichment of signaling pathways involved in 96 patients with AMI during the acute phase （Benjamini P0.01）.KEGG pathway enrichment analysis showed that 6 signaling pathway involved in the process of AMI （Benjamini P0.01）.It was proved that its related genes CXCR1,CXCR2,Src,Raf and ERK1/2 expression were consistent with the chip,and were upregulated.When compared with control group,CXCR1,CXCR2,Src,Raf and ERK1/2 expression in AMI group were significantly higher（P0.001）.PI3K expression also tended to increase.Conclusions Many signaling pathways involved in AMI in acute phase of the process,including Chemokine signaling pathway,and it is closely related to the pathogenesis of AMI.

关 键 词：心肌梗死 冠状动脉 基因 寡核苷酸序列分析 Chemokine信号通路 

分 类 号：R542.22[医药卫生—心血管疾病]