急性心肌梗死合并收缩功能障碍患者血清miR-125b与依普利酮抗纤维化反应的关系

Relationship between serum miR-125b and antifibrotic response to eplerenone in patients with acute myocardial infarction complicated with systolic dysfunction

目的探讨血清miR-125b对依普利酮抗纤维化治疗反应评估的价值。方法前瞻性纳入2020年8月9日—2021年4月1日在太原市急救中心心内科接受依普利酮治疗的89例急性心肌梗死(AMI)伴或不伴ST段抬高且伴有左心室收缩功能障碍患者。采集受试者依普利酮治疗前和治疗6个月后的外周血浆样本。二维超声心动和多普勒超声心动图评估心脏收缩功能。采用实时荧光定量PCR法检测血浆中循环miR-125b表达水平;采用放射免疫测定法和酶联免疫吸附法分别检测血清Ⅲ型胶原氨基末端前肽(PⅢNP)和Ⅰ型胶原羧基末端前肽(PⅠCP)水平,计算基线至第6个月血清PⅢNP(?PⅢNP)和PⅠCP(?PⅠCP)水平变化。并记录依普利酮治疗6个月期间患者的主要不良心血管事件(MACEs)。结果依普利酮治疗6个月后,AMI患者收缩压与超声心动图参数较基线值显著改善(P<0.05),收缩压、血清PⅢNP和PⅠCP水平降低(P<0.05),但同时血钾和血钠浓度有所升高(P<0.05)。其中50例患者第6个月时血清PⅢNP水平值较基线值绝对减少,纳入PⅢNP降低亚组,其他39例患者?PⅢNP≤0,被纳入PⅢNP稳定/增加亚组。Logistic回归分析显示,女性、经皮冠状动脉介入治疗、血清miR-125b是PⅢNP降低的独立预测因子(P<0.05)。Spearman等级相关系数分析显示,PⅢNP降低的患者基线血清miR-125b与?PⅢNP(rs=-0.566,P<0.001)和?PⅠCP(rs=-0.524,P<0.001)存在负相关关系。进一步校正危险因素后,基线血清miR-125b仍是影响血清PⅢNP和PⅠCP降低程度的独立负相关因素(P<0.05)。此外,在AMI患者中,PⅢNP降低的患者累积MACEs发生率更低(调整后HR=0.431,95%CI:0.129~1.440,P=0.171),同样血清miR-125b水平>2.23患者无MACEs事件累积生存率更低(Log rank=32.568,P<0.001)。结论血清miR-125b高表达水平有助于识别依普利酮抗纤维化作用更显著的AMI患者。

Objective To investigate the predictive value of serum miR-125b for the antifibrotic response to eplerenone.Methods From August 9,2020 to April 1,2021,89 patients with acute myocardial infarction(AMI)with or without STsegment elevation and with left ventricular systolic dysfunction who received eplerenone treatment in the Department of Cardiology of our hospital were prospectively included.Collected the peripheral blood samples before and 6 months after eplenone treatment.Thoracic 2-D and Doppler echocardiography were used to assess systolic function.Real-time quantitative fluorescent PCR was used to detect the expression level of serum miR-125b.Serum TypeⅢcollagen amino terminal propeptide(PⅢNP)and typeⅠcollagen carboxyl terminal propeptide(PⅠCP)levels were measured by radioimmunoassay and enzyme-related immunosorbent assay respectively,to calculate the changes of serum PⅢNP(ΔPⅢNP)and PⅠCP(ΔPⅠCP)levels from baseline to the 6th month.Moreover,the major adverse cardiovascular events(MACEs)during 6 months were recorded.Results After 6 months of treatment with eplerenone,systolic blood pressure and echocardiographic parameters of AMI patients were significantly improved compared with the baseline values(P<0.05),and systolic blood pressure,serum PⅢNP and PⅠCP levels were decreased(P<0.05).The serum PⅢNP level of 50 patients at the 6th month was absolutely lower than the baseline value,and they were included in the PⅢNP reduction subgroup.The other 39 patients withΔPⅢNP≤0 were included in the PⅢNP stable/elevated subgroup.Logistic regression analysis showed that female,PCI and serum miR-125b were independent predictors of PⅢNP reduction(P<0.05).Spearman grade correlation coefficient analysis showed that baseline serum miR-125b in patients with decreased PⅢNP was negativelycorrelatedwithΔPⅢNP(rs=-0.566,P<0.001)andΔPⅠCP(rs=-0.524,P<0.001).In addition,among AMI patients,patients with reduced PⅢNP had a lower cumulative MACEs incidence(adjusted HR=0.431,95%CI:0.129-1.440,P=0.171),and similarly,patients with serum miR-125b>2.23 had a lower cumulative survival rate without MACEs events(log rank=32.568,P<0.001).Conclusion HighexpressionlevelsofserummiR-125b contributed to identify subgroups of AMI patients with more significant antifibrotic effects of eplerenone.