缺血性心肌病患者外周血MicroRNA-182、CITED2及HIF-1的表达及相关性研究  

Expression of circulating microRNA-182,CITED2 and HIF-1 in ischemic cardiomyopathy and their correlation

作　　者：曾晓聪[1] 李醒三[1] 文宏[1] ZENG Xiaocong LI Xingsan WEN Hong(Department of Cardiology, the First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China)

机构地区：[1]广西医科大学第一附属医院心血管内科,南宁530021

出　　处：《临床心血管病杂志》2017年第2期119-122,共4页Journal of Clinical Cardiology

基　　金：广西壮族自治区卫生厅自筹经费科研课题(No:Z2011318);广西医科大学青年科学基金(No:GXMUYSF2014028)

摘　　要：目的:探讨microRNA-182(miR-182)、cAMP应答元件结合蛋白反式作用因子(CITED2)及低氧诱导因子-1(HIF-1)在缺血性心肌病(ICM)患者外周血中的表达及相关性。方法:收集本院46例ICM患者设为ICM组,同期选择32例健康者为对照组。分析2组一般资料及心脏功能指标[氨基末端B型脑钠肽前体(NTproBNP)、左室射血分数(LVEF)、6min步行实验(6MWT)距离];用实时荧光定量聚合酶链式反应法(qRT-PCR)检测血浆miR-182的含量,采用ELISA法测定血清CITED2和HIF-1水平,并观察ICM组治疗前及治疗3个月后上述指标的变化;分析ICM患者血浆miR-182水平与有关因素的相关性。结果:ICM组治疗前CITED2、LVEF及6MWT距离明显低于对照组,NT-proBNP、HIF-1及miR-182表达明显高于对照组,差异均有统计学意义(P<0.01)。与ICM组治疗前比较,ICM组治疗后CITED2、LVEF及6MWT距离明显升高,NT-proBNP、HIF-1及miR-182显著降低,差异均有统计学意义(P<0.01)。ICM组治疗前血浆miR-182的水平与CITED2、LVEF及6MWT距离成负相关(r=-0.427、-0.351、-0.298,P<0.05);ICM组治疗前血浆miR-182水平与HIF-1成正相关(r=0.337,P<0.05)。结论:外周血miR-182水平可作为ICM诊断及进行风险评估的生物标志物。miR-182可能通过其靶蛋白CITED2上调HIF-1,参与调控ICM的发生及发展。Objective：To explore the expression of circulating microRNA-182（miR-182）,CBP/p300 interacting transactivators with ED-rich termini 2（CITED2）,hypoxia-inducible factor-1（HIF-1）in ischemic cardiomyopathy（ICM）,and to study their correlation.Method：Thirty two healthy volunteers and 46 ICM patients were enrolled,and their general clinical data and cardiac functional parameters,including N-terminal pro-B-type natriuretic peptide（NTproBNP）,left ventricular ejection fraction（LVEF）and the 6-minute walk test（6MWT）distance,were analyzed.The levels of blood plasma miR-182 in all subjects were detected by real time quantitative polymerase chain reaction（qRTPCR）.Serum levels of CITED2 and HIF-1were detected by enzyme linked immunosorbent assay（ELISA）,and their correlation with miR-182 was analyzed.Treatment lasted for 3months.Level of NT-proBNP,CITED2,HIF-1,miR-182,6MWT and LVEF in ICM group were observed before and after treatment.Result：Before treatment,the 6MWT distance,LVEF and CITED2 levels in ICM group were significantly lower than those in the control group（P〈0.01）.The NT-proBNP、HIF-1and miR-182 levels in ICM group were significantly higher than those in the control group（P〈0.01）.After 3months treatment,level of CITED2,6min walk distance and LVEF of patients in ICM group were significantly increased（P〈0.01）,and level of plasma NT-proBNP HIF-1and miR-182 in ICM group were significantly decreased（P〈0.01）.Plasma miR-182 was negatively correlated with CITED2,LVEF and the 6MWT distance in group ICM（r=-0.427,-0.351,-0.298,P〈0.05）.Plasma miR-182 was positively correlated with HIF-1in group ICM（r=0.337,P〈0.05）.Conclusion：Circulating miR-182 can be used as a new biomarker for ICM diagnosis and its risk evaluation.MiR-182 may upregulate the expression of HIF-1by depressing CITED2,which might play an important role in the pathogenesis of ICM.

关 键 词：缺血性心肌病 microRNA-182 cAMP应答元件结合蛋白反式作用因子 低氧诱导因子-1 

分 类 号：R541.1[医药卫生—心血管疾病]