血清miR-155及缺氧诱导因子1α的表达对急性脑梗死的诊断价值

Diagnostic value of serum miR-155 and hypoxia-inducible factor 1α in acute cerebral infarction

目的探讨血清miR-155及其靶基因缺氧诱导因子1α(hypoxiainducible factor 1α,HIF1A)与急性脑梗死(acute cerebral infarction,ACI)的相关性,探寻与ACI诊断及治疗有关的潜在血清生物标志物。方法实时荧光定量聚合酶链反应(real time-PCR)法检测ACI患者和健康对照组血清miR-23b、miR-106b、miR-130a、miR-155和miR-425的表达水平,使用miRBase和TargetScan数据库推测靶基因,并应用双荧光素酶报告和蛋白质印迹分析的办法验证,应用多变量Logistic回归分析等进行分析。结果与健康对照组相比,ACI患者血清miR-155水平显著上调(P<0.05);经验证HIF1A是miR-155的靶基因;ACI患者血清HIF1A mRNA的表达水平显著下调(P<0.05),与miR-155的表达呈显著负相关(P<0.05);单独或联合存在的miR-155高表达和HIF1A mRNA低表达均与ACI患者的高总胆固醇(P<0.05)、高LDL(P<0.05)和低HDL(P<0.05)有显著相关性;此外,高表达的miR-155(P<0.05)、低表达的HIF1A mRNA(P<0.05),或者高miR-155和低HIF1A mRNA的联合表达都可能是检测ACI的指标。结论血清miR-155上调及其靶基因HIF1A的下调与ACI具有相关性,可能对开发针对ACI的miRNA定向诊断有参考意义。

Objective To investigate the relationship between serum miR-155 and its target hypoxia inducible factor 1α(HIF1A)and acute cerebral infarction(ACI),and to explore potential serum biomarkers related to ACI.Methods Real-time fluorescence quantitative polymerase chain reaction(PCR)was used to detect the expression levels of serum miR-23b,miR-106b,miR-130a,miR-155 and miR-425 in ACI patients and healthy controls.The target gene was postulated by using miRBase and TargetScan database and verified by dual luciferase reporter and Western blot analysis,and analyzed by multivariate Logistic regression analysis.Results Compared with healthy controls,serum miR-155 levels were significantly up-regulated in ACI patients(P<0.05).HIF1A was the target gene of miR-155.The expression level of serum HIF1A mRNA in ACI patients was significantly down-regulated(P<0.05).There was a significant negative correlation with the expression of miR-155(P<0.05).High expression of miR-155 and low expression of HIF1A mRNA alone or in combination with high cholesterol(P<0.05)and high LDL in ACI patients(P<0.05)and low HDL(P<0.05);in addition,high expression of miR-155(P<0.05),low expression of HIF1A mRNA(P<0.05),or high miR-155 and low HIF1A mRNA Combined expression may be an indicator for detecting the presence of ACI.Conclusion Up-regulation of serum miR-155 and down-regulation of its target gene HIF1A are associated with ACI,which may be useful for the development of targeted miRNA diagnosis for ACI.