心房颤动患者血浆miRNA-1和miRNA-155检测在复律后复发预测的应用研究
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摘要
目的探讨血浆miRNA-1和miRNA-155检测在心房颤动患者复律后复发预测中的临床应用价值。方法收集2015年10月~2017年11月于西安市第八医院和咸阳市中心医院心内科住院治疗的110例房颤患者的血液及临床资料(复律组110例,复发组30例,未复发组80例),比较分析三组患者血浆miRNA-1和miRNA-155表达水平的变化与房颤复发的关系。两标志物的表达采用实时逆转录-聚合酶链反应(RT-PCR)技术检测。应用心动超声仪评价患者的左房内径及左心室射血分数。采用罗氏MODULARP800全自动生化分析仪检测患者的空腹血糖及总胆固醇水平。建立受试者工作特征曲线(ROC曲线)评价miRNA-1和miRNA-155在房颤复发中的临床意义。结果血浆miRNA-1和miRNA-155在未复发组、复律组和复发组的水平分别为0.38±0.09,0.39±0.08,0.82±0.15和0.87±0.17,0.85±0.18,0.21±0.05。它们在复发组的表达与未复发组和复律组分别比较明显上调、下调(t=21.37,20.57,均P<0.01;t=18.77,11.71,均P<0.01),而在未复发组与复律组的表达比较差异无统计学意义(t=0.67,0.54,均P>0.05)。房颤患者的收缩压、血清总胆固醇水平(TC)、左房内径、空腹血糖水平(FBG)和左室射血分数(EF)分别在未复发组、复律组和复发组的检测结果为(133±7mmHg,3.87±0.73mmol/L,44.97±6.82mm,4.13±0.57mmol/L,61.20%±7.38%),(134±6mmHg,3.98±0.70mmol/L,45.50±6.72mm,4.17±0.46mmol/L,61.07%±7.19%),(145±7mmHg,4.03±0.71mmol/L,58.97±7.33mm,4.20±0.50mmol/L,60.30%±7.21%)。复发组的左心房内径和收缩压分别与复律组和未复发组比较显著增高(t=6.69,10.23,P<0.01;t=8.42,15.53,P<0.01);而复律组的两项指标分别与未复发组比较差异均无统计学意义(t=0.73,0.27,均P>0.05);各组间的TC,FBG和EF比较,差异均无统计学意义(t=0.58,0.61,0.52,均P>0.05;t=0.65,0.58,0.41,均P>0.05;t=0.61,0.41,0.52,均P>0.05)。在复发组中,miRNA-1和miRNA-155表达具有负相关(r=-0.673,P<0.01),且它们分别与左心房内径、收缩压也具有相关性(r=0.528,-0.537),均P<0.01。ROC曲线的分析中,复发组分别以复律组和未复发组为参照,血浆miRNA-1的AUC分别为0.743(95%CI:0.627~0.839),P<0.01;0.730(95%CI:0.21~0.826),P<0.01,血浆miRNA-155的AUC分别为0.703(95%CI:0.628~0.837),P<0.01;0.685(95%CI:0.603~0.813),P<0.01。结论血浆miRNA-1和miRNA-155检测可应用于房颤患者复律后复发的预测,并成为房颤复发有效的预警标志物和干预靶点。
Objective To investigate the application of plasma miRNA-1 and miRNA-155 in predicting recurrence after cardioversion for atrial fibrillation.Methods The blood and clinical data of 110 patients with atrial fibrillation in Department of Cardiology hospitalized from the Eighth Hospital of Xi'an and Central Hospital of Xianyang from October 2015 to November 2017 were collected(110 cases in cardioversion group,30 cases in relapse group and 80 cases in non-recurrence group).The relationship between the changes of miRNA-1 and miRNA-155 expression levels in plasma in the three groups,and the recurrence of atrial fibrillation were compared and analyzed.Expression of two markers was detected via real-time reverse transcription polymerase chain reaction(RT-PCR).The left atrial diameter and left ventricular ejection fraction were evaluated by echocardiography.The fasting blood glucose and total cholesterol were detected using Roche MODULARP800 automatic biochemical analyzer.The receiver operating characteristic curve(ROC curve)was established to evaluate the clinical significance of miRNA-1 and miRNA-155 in the recurrence of atrial fibrillation.Results The levels of plasma miRNA-1 and miRNA-155 in the non recurrent group,the cardioversion group and the recurrent group were(0.38±0.09,0.39±0.08,0.82±0.15)and(0.87±0.17,0.85±0.18,0.21±0.05),which in the recurrent group was significantly up and down compared with in the non-recurrent and cardioversion groups,respectively(t=21.37,20.57,P<0.01;t=18.77,11.71,P<0.01).Nevertheless,no differences of the two markers were observed between the non recurrent group and the cardioversion group(t=0.67,0.54,P>0.01).These outcomes of systolic pressure,serum total cholesterol level(TC),left atrial diameter,fasting blood glucose level(FBG)and left ventricular ejection fraction(EF)in non recurrent group,cardioversion group and recurrent group were(133±7 mmHg,3.87±0.73 mmol/L,44.97±6.82 mm,4.13±0.57 mmol/L,61.20% ±7.38%),(134±6 mmHg,3.98±0.70 mmol/L,45.50±6.72 mm,4.17±0.46 mmol/L,61.07%±7.19%),(145±7 mmHg,4.03±0.71 mmol/L,58.97±7.33 mm,4.20±0.50 mmol/L,60.30%±7.21%).Interestingly,these evident incresces of left atrial diameter and systolic pressure were clarified for the recurrent patients following these statistical differences(t=6.69,10.23,P<0.05;t=8.42,15.53,P<0.05),and observations of no differences were described for them between the cardioversion group and the non recurrent group(t=0.27,0.73,P>0.05).In addition,these presences of TC,FBG and EF in the three group were shown to be not statistically significant(t=0.58,0.61,0.52,P>0.05;t=0.65,0.58,0.41,P>0.05;t=0.61,0.41,0.52,P>0.05).In the recurrent group,the expression of miRNA-1 and miRNA-155 was revealed to present a negative correlation(r=-0.673,P<0.01),and to be correlated with the left atrium diameter and systolic pressure,respectively(r=0.528,-0.537,P<0.01).According to analysis of ROC curve,the data in the recurrence group was taken these in the cardioversion group and the non recurrent group as a reference,the AUC of plasma miRNA-1 was 0.743(95%CI:0.627~0.839),P<0.01;0.730(95%CI:0.21~0.826),P<0.01,and the AUC of the plasma miRNA-155 was0.703(95%CI:0.628~0.837),P<0.01;0.685(95%CI:0.603~0.813),P<0.01,respectively.Conclusion Detection of plasma miRNA-1 and miRNA-155 can be used predicting recurrence of atrial fibrillation patients after cardioversion,and become an effective early warning marker and intervention target for recurrence of atrial fibrillation.
Objective To investigate the application of plasma miRNA-1 and miRNA-155 in predicting recurrence after cardioversion for atrial fibrillation.Methods The blood and clinical data of 110 patients with atrial fibrillation in Department of Cardiology hospitalized from the Eighth Hospital of Xi'an and Central Hospital of Xianyang from October 2015 to November 2017 were collected(110 cases in cardioversion group,30 cases in relapse group and 80 cases in non-recurrence group).The relationship between the changes of miRNA-1 and miRNA-155 expression levels in plasma in the three groups,and the recurrence of atrial fibrillation were compared and analyzed.Expression of two markers was detected via real-time reverse transcription polymerase chain reaction(RT-PCR).The left atrial diameter and left ventricular ejection fraction were evaluated by echocardiography.The fasting blood glucose and total cholesterol were detected using Roche MODULARP800 automatic biochemical analyzer.The receiver operating characteristic curve(ROC curve)was established to evaluate the clinical significance of miRNA-1 and miRNA-155 in the recurrence of atrial fibrillation.Results The levels of plasma miRNA-1 and miRNA-155 in the non recurrent group,the cardioversion group and the recurrent group were(0.38±0.09,0.39±0.08,0.82±0.15)and(0.87±0.17,0.85±0.18,0.21±0.05),which in the recurrent group was significantly up and down compared with in the non-recurrent and cardioversion groups,respectively(t=21.37,20.57,P<0.01;t=18.77,11.71,P<0.01).Nevertheless,no differences of the two markers were observed between the non recurrent group and the cardioversion group(t=0.67,0.54,P>0.01).These outcomes of systolic pressure,serum total cholesterol level(TC),left atrial diameter,fasting blood glucose level(FBG)and left ventricular ejection fraction(EF)in non recurrent group,cardioversion group and recurrent group were(133±7 mmHg,3.87±0.73 mmol/L,44.97±6.82 mm,4.13±0.57 mmol/L,61.20% ±7.38%),(134±6 mmHg,3.98±0.70 mmol/L,45.50±6.72 mm,4.17±0.46 mmol/L,61.07%±7.19%),(145±7 mmHg,4.03±0.71 mmol/L,58.97±7.33 mm,4.20±0.50 mmol/L,60.30%±7.21%).Interestingly,these evident incresces of left atrial diameter and systolic pressure were clarified for the recurrent patients following these statistical differences(t=6.69,10.23,P<0.05;t=8.42,15.53,P<0.05),and observations of no differences were described for them between the cardioversion group and the non recurrent group(t=0.27,0.73,P>0.05).In addition,these presences of TC,FBG and EF in the three group were shown to be not statistically significant(t=0.58,0.61,0.52,P>0.05;t=0.65,0.58,0.41,P>0.05;t=0.61,0.41,0.52,P>0.05).In the recurrent group,the expression of miRNA-1 and miRNA-155 was revealed to present a negative correlation(r=-0.673,P<0.01),and to be correlated with the left atrium diameter and systolic pressure,respectively(r=0.528,-0.537,P<0.01).According to analysis of ROC curve,the data in the recurrence group was taken these in the cardioversion group and the non recurrent group as a reference,the AUC of plasma miRNA-1 was 0.743(95%CI:0.627~0.839),P<0.01;0.730(95%CI:0.21~0.826),P<0.01,and the AUC of the plasma miRNA-155 was0.703(95%CI:0.628~0.837),P<0.01;0.685(95%CI:0.603~0.813),P<0.01,respectively.Conclusion Detection of plasma miRNA-1 and miRNA-155 can be used predicting recurrence of atrial fibrillation patients after cardioversion,and become an effective early warning marker and intervention target for recurrence of atrial fibrillation.
引文
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[8]Lorenzen JM,Schauerte C,Hübner A,et al.Osteopontin is indispensible for AP1-mediated angiotensin II-related miR-21transcription during cardiac fibrosis[J].Eur Heart J,2015,36(32):2184-2196.
[9]Papageorgiou N,Tsalamandris S,Giolis A,et al.MicroRNAs in cardiovascular disease:Perspectives and reality[J].Cardiol 2016,24(3):110-118.
[10]赵晟,杨诺,岳语喃,等.射频消融术改变心房颤动患者外周血微小RNA表达谱[J].中华老年心脑血管病杂志,2015,17(7):725-731.Zhao S,Yang N,Yue YN,et al.Radiofrequency ablation of atrial fibrillation rebalances atrial ion current remodeling by regulating miRNAs[J].Chinese Journal Geriatric Heart Brain and Vessel,2015,17(7):725-731.
[11]Wu A,Lou L,Zhai J,et al.miRNA expression profile and effect of wenxin granule in rats with ligation-induced myocardial infarction[J].Int J Genomics,2017,2017:2175871.
[12]Wu A,Zhao M,Lou L,et al.Effect of wenxin granules on gap junction and MiR-1in rats with myocardial infarction[J].Biomed Res Int,2017,2017(5):3495021.
[2]蒋智渊,钟国强,肖飞,等.微小RNA-101在心房颤动心房纤维化中的作用[J].实用医学杂志,2015,31(6):890-893.Jiang ZY,Zhong GQ,Xiao F,et al.Effect of miRNA-101on atrial fibrillation in human chronic atrial fibrillation[J].The Journal of Practical Medicine,2015,31(6):890-893.
[3]Zhao J,Hansen JB,Wang Y,et al.Three-dimensional integrated functional,structural,and computational mapping to define the structural“Fingerprints”of heart-specific atrial fibrillation drivers in human heart ex vivo[J].J Am Heart Assoc,2017,6(8):e005922.
[4]Dai H,Wang X,Yin S,et al.Atrial fibrillation promotion in a rat model of rheumatoid arthritis[J].J Am Heart Assoc,2017,6(12):e007320.
[5]程涛,黄刚.血清miRNA-21,miRNA-126表达在诊断PCI术后冠状动脉再狭窄的临床应用价值[J].现代检验医学杂志,2018,33(1):59-62,66.Cheng T,Huang G.Clinical value of serum miRNA-21and miRNA-126expression in diagnosis of the coronary artery restenosis after PCI[J].Journal of Modern Laboratory Medicine,2018,33(1):59-62,66.
[6]崔淯夏,苏迎,李龙,等.心房颤动射频消融手术可逆转微小RNA的调控异常[J].中华心血管病杂志,2015,43(12):1051-1056.Cui YX,Su Y,Li L,et al.Radiofrequency ablation can reverse the abnormal ciycalating microRNA expression changes in patients with atrid fibrillation[J].Chinese Journal of cardiovascular disease,2015,43(12):1051-1055.
[7]Wei Y,Yan X,Yan L,et al.Inhibition of microRNA-155ameliorates cardiac fibrosis in the process of angiotensin II-induced cardiac remodeling[J].Mol Med Rep,2017,16(5):7287-7296.
[8]Lorenzen JM,Schauerte C,Hübner A,et al.Osteopontin is indispensible for AP1-mediated angiotensin II-related miR-21transcription during cardiac fibrosis[J].Eur Heart J,2015,36(32):2184-2196.
[9]Papageorgiou N,Tsalamandris S,Giolis A,et al.MicroRNAs in cardiovascular disease:Perspectives and reality[J].Cardiol 2016,24(3):110-118.
[10]赵晟,杨诺,岳语喃,等.射频消融术改变心房颤动患者外周血微小RNA表达谱[J].中华老年心脑血管病杂志,2015,17(7):725-731.Zhao S,Yang N,Yue YN,et al.Radiofrequency ablation of atrial fibrillation rebalances atrial ion current remodeling by regulating miRNAs[J].Chinese Journal Geriatric Heart Brain and Vessel,2015,17(7):725-731.
[11]Wu A,Lou L,Zhai J,et al.miRNA expression profile and effect of wenxin granule in rats with ligation-induced myocardial infarction[J].Int J Genomics,2017,2017:2175871.
[12]Wu A,Zhao M,Lou L,et al.Effect of wenxin granules on gap junction and MiR-1in rats with myocardial infarction[J].Biomed Res Int,2017,2017(5):3495021.