射血分数保留性心力衰竭患者血清miR-146a,IRAK-1表达水平与血管内皮功能、心室重构的相关性分析

Correlation Analysis of Serum miR-146a,IRAK-1 Expression Levels with Vascular Endothelial Function and Ventricular Remodeling in Patients with Ejection Fraction Preserved Heart Failure

目的探讨射血分数保留性心力衰竭(heart failure with preserved ejection fraction,HFpEF)患者血清微小RNA(micro RNA,miR)-146a、白介素1受体相关激酶1(interleukin-1 receptor-associated kinase 1,IRAK-1)表达水平及其与血管内皮功能、心室重构的相关性。方法选择2021年6月~2022年3月在内蒙古医科大学附属医院收治的93例HFpEF患者为观察对象,选择同期门诊体检健康者(无心血管病史)90例为对照组,收集患者资料,采用实时荧光定量PCR(quantitative real-time PCR,q RT-PCR)检测血清mi R-146a和IRAK-1 mRNA表达,采用酶联免疫吸附试验(enzyme linked immunosorbent assay,ELISA)法检测血清内皮素-1(endothelin-1,ET-1)水平,化学发光法检测血清一氧化氮(nitric oxide,NO)水平,超声心动图检查左室射血分数(LVEF)、二尖瓣口舒张早期最大血流速度E峰与舒张晚期最大血流速度A峰的比值(E/A)、左心室舒张末期内径(LVEDD)、左心房内径(LAD)和左室质量指数(LVMI)。Pearson法分析HFpEF患者血清miR-146a和IRAK-1 mRNA表达水平的相关性及miR-146a,IRAK-1与血管内皮功能、心室重构相关性指标的相关性,ROC曲线分析血清miR-146a和IRAK-1对HFpEF的诊断价值。结果与对照组比较,HFpEF组血清miR-146a(2.13±0.35 vs 1.05±0.21)表达水平升高,IRAK-1 mRNA(0.65±0.10 vs 1.03±0.12)表达水平降低,差异有统计学意义(t=25.209,23.302,均P<0.05);HFpEF患者血清miR-146a与IRAK-1 mRNA水平呈负相关(r=-0.473,P<0.001),血清miR-146a与ET-1,LVEDD,LAD,LVMI呈正相关(r=0.501,0.556,0.391,0.601,均P<0.001),与血清NO,LVEF,E/A呈负相关(r=-0.453,-0.623,-0.613,均P<0.001);IRAK-1 mRNA与血清ET-1,LVEDD,LAD,LVMI呈负相关(r=-0.369,-0.478,-0.551,-0.457,均P<0.001),与血清NO,LVEF,E/A呈正相关(r=0.447,0.605,0.567,均P<0.001)。血清miR-146a,IRAK-1联合诊断HFpEF的AUC显著高于miR-146a,IRAK-1单独诊断(Z=2.122,2.067,P=0.033,0.038)。结论HFpEF患者血清miR-146a表达水平升高,IRAK-1表达水平降低,与血管内皮功能、心室重构相关,可能成为HFpEF诊断与病情评估的指标。

Objective To investigate the expression levels of serum microRNA(miR)-146a and interleukin-1 receptorassociated kinase 1(IRAK-1)in patients with heart failure with preserved ejection fraction(HFpEF)and their correlation with vascular endothelial function and ventricular remodeling.Methods 93 HFpEF patients admitted to the Affiliated Hospital of Inner Mongolia Medical University from June 2021 to March 2022 were selected as observation objects.A total of 90 healthy people(with no history of cardiovascular disease)were selected as the control group.The data of patients were collected,Quantitative Real-time PCR(qRT-PCR)was used to detect the expression of serum miR-146a and IRAK-1 mRNA,Enzyme linked immunosorbent assay(ELISA)was used to detect the level of serum endothelin-1(ET-1),chemiluminescent immunoassay methods were used to detect the level of serum nitric oxide(NO),echocardiography was used to examine left ventricular ejection fraction(LVEF),the ratio of the maximum early diastolic flow velocity of the mitral valve E-peak to the maximum late-diastolic flow velocity of the A-peak(E/A),the left ventricular end-diastolic diameter(LVEDD),left atrial diameter(LAD),and left ventricular mass index(LVMI).Pearson was used to analyze the correlation of serum miR-146a and IRAK-1 mRNA expression levels in HFpEF patients and the correlation of miR-146a and IRAK-1 with vascular endothelial function and ventricular remodeling-related indicators,ROC curve was used to analyze the diagnostic value of serum miR-146a and IRAK-1 for HFpEF.Results Compared with the control group,the expression level of miR-146a(2.13±0.35 vs 1.05±0.21)in serum of HFpEF group was increased,and the expression level of IRAK-1 mRNA(0.65±0.10 vs 1.03±0.12)was decreased,with statistical significance(t=25.209,23.302,all P<0.05).Serum miR-146a and IRAK-1 levels in HFpEF patients were negatively correlated(r=-0.473,P<0.001).Serum miR-146a was positively correlated with ET-1,LVEDD,LAD and LVMI(r=0.501,0.556,0.391,0.601,all P<0.001),negatively correlated with serum NO,LVEF and E/A(r=-0.453,-0.623,-0.613,all P<0.001),IRAK-1 mRNA was negatively correlated with serum ET-1,LVEDD,LAD and LVMI(r=-0.369,-0.478,-0.551,-0.457,all P<0.001),and positively correlated with serum NO,LVEF and E/A(r=0.447,0.605,0.567,all P<0.001).The AUC of serum miR-146a and IRAK-1 in the diagnosis of HFpEF was significantly higher than that of miR-146a and IRAK-1 alone(Z=2.122,2.067,P=0.033,0.038).Conclusion The expression level of serum miR-146a in HFpEF patients was increased,and the expression level of IRAK-1 was decreased,and may become an indicator of diagnosis and disease evaluation of HFpEF.