MicroRNA-126、microRNA-328与急性非ST段抬高型心肌梗死患者心肌损伤标志物的相关性

Correlation of microRNA-126 and microRNA-328 with myocardial injury marker levels in patients with acute non-ST-segment elevation myocardial infarction

摘要:

目的 研究血清microRNA-126（miR-126）、microRNA-328（miR-328）与急性非ST段抬高型心肌梗死（NSTEMI）患者心肌损伤标志物的相关性。方法 选取2021年1月—2022年1月宁夏医科大学总医院收治的191例急性NSTEMI患者为观察组，另选取同期该院门诊体检健康的180例志愿者为对照组。比较两组的心肌损伤标志物［脑钠肽（BNP）、肌酸激酶同工酶（CK-MB）、乳酸脱氢酶（LDH）、心肌肌钙蛋白I（cTnI）］水平，以及miR-126、miR-328表达的差异。绘制受试者工作特征（ROC）曲线分析BNP、CK-MB、LDH、cTnI、miR-126、miR-328预测NSTEMI的价值。参照全球冠状动脉事件登记（GRACE）评分标准，将急性NSTEMI患者分为低危组、中危组及高危组，比较3组BNP、CK-MB、LDH、cTnI、miR-126、miR-328的差异。采用Pearson相关系数分析BNP、CK-MB、LDH、cTnI与miR-126、miR-328的相关性。结果 观察组BNP、CK-MB、LDH、cTnI水平及miR-328 mRNA相对表达量高于对照组（P <0.05），miR-126 mRNA相对表达量低于对照组（P <0.05）。ROC曲线分析结果显示，BNP ≥ 1 149.684 ng/L、CK-MB ≥ 34.760 ng/mL、LDH ≥ 812.535 u/L、cTnI ≥ 3.583 μg/L、miR-126 ≤ 26.825、miR-328 ≥ 1.215是NSTEMI的最佳截断值，敏感性分别为84.2%（95% CI：0.714，0.854）、84.7%（95% CI：0.723，0.921）、83.7%（95% CI：0.741，0.882）、67.9%（95% CI：0.595，0.789）、87.2%（95% CI：0.623，0.932）、77.9%（95% CI：0.745，0.836），特异性分别为82.8%（95% CI：0.653，0.912）、83.9%（95% CI：0.675，0.931）、83.9%（95% CI：0.741，0.963）、74.4%（95% CI：0.628，0.844）、87.9%（95%CI：0.573，0.917）、82.8%（95%CI：0.749，0.901）。高危组BNP、CK-MB、LDH、cTnI水平及miR-328 mRNA相对表达量较低危组、中危组升高（P <0.05），miR-126 mRNA相对表达量较低危组、中危组降低（P <0.05）。Pearson相关性分析结果显示，miR-126与BNP、CK-MB、LDH、cTnI呈负相关（P <0.05），miR-328与BNP、CK-MB、LDH、cTnI呈正相关（P <0.05）。结论 NSTEMI患者的BNP、CK-MB、LDH、cTnI水平及miR-126、miR-328 mRNA相对表达量与健康人群有差异，并随NSTEMI病情进展而变化。miR-126、miR-328与BNP、CK-MB、LDH、cTnI相关，提示miR-126、miR-328有望成为NSTEMI早期诊断的新型标志物。

Abstract:

Objective To study the relationship between serum microRNA-126 (miR-126), serum microRNA-328 (miR-328), and myocardial injury markers in patients with acute non-ST-segment elevation myocardial infarction (NSTEMI).Methods A total of 191 NSTEMI patients admitted from January 2021 to January 2022 were selected as the observation group, and 180 healthy volunteers who underwent physical examination in outpatient department during the same period were selected as the control group. The levels of creatine kinase isoenzyme (CK-MB), cardiac troponin I (cTnI), lactate dehydrogenase (LDH), brain natriuretic peptide (BNP), miR-126, and miR-328 were compared between the two groups. Under ROC analysis, the predictive value of BNP, CK-MB, LDH, cTnI, miR-126, and miR-328 for non-STEMI was determined. Non-stemi patients were divided into low-risk group, medium-risk group, and high-risk group according to global coronary event registry (GRACE score). The correlation of BNP, CK-MB, LDH, and cTnI wirh miR-126 and miR-328 was analyzed by Person correlation coefficient.Results Compared with the control group, BNP, CK-MB, LDH, cTnI and miR-328 in the observation group were higher than those in the control group, and miR-126 was lower than that in the control group (P < 0.05). ROC analysis showed that BNP ≥ 1 149.684 ng/L, CK-MB ≥ 34.760 ng/mL, LDH ≥ 812.535 u/L, cTnI ≥ 3.583 μg/L, miR-126 ≤26.825, miR-328 ≥1.215 were the best cut-off values for non-STEMI. The sensitivity was 84.2% (95% CI: 0.714, 0.854), 84.7% (95% CI: 0.723, 0.921), 83.7% (95% CI: 0.741, 0.882), 67.9% (95% CI: 0.595, 0.789), 87.2% (95% CI: 0.623, 0.932), and 77.9% (95% CI: 0.745, 0.836), and specificity was 82.8% (95% CI: 0.653, 0.912), 83.9 %(95% CI: 0.675, 0.931), 83.9% (95% CI: 0.741, 0.963), 74.4% (95% CI: 0.628, 0.844), 87.9% (95% CI: 0.573, 0.917), and 82.8% (95% CI: 0.749, 0.901), respectively. There were significant differences in BNP, CK-MB, LDH, cTnI, miR-126 and miR-328 in patients with different severity of non-STEMI (P < 0.05). Compared with the low-risk and medium-risk groups, the levels of BNP, CK-MB, LDH, cTnI, and miR-328 were higher and the levels of miR-126 were lower in the high-risk group (P < 0.05). The correlation analysis showed that miR-126 was negatively correlated with BNP, CK-MB, LDH, and cTnI, while miR-328 was positively correlated with BNP, CK-MB, LDH, and cTnI (P < 0.05).Conclusion The myocardial injury markers and the levels of miR-126 and miR-328 in non-STEMI patients were significantly different from those in healthy people, and correlation analysis confirmed that miR-126 was negatively correlated with BNP, CK-MB, LDH, and cTnI, and miR-328 was positively correlated with BNP, CK-MB, LDH, and cTnI.