文章摘要
急性冠脉综合征患者外周血miR-378a-3p的表达及其诊断价值
Expression of miR-378a-3p in Peripheral Blood of Patients With Acute Coronary Syndrome and its Diagnostic Value
投稿时间:2024-03-08  修订日期:2024-03-08
DOI:
中文关键词: 急性冠脉综合征  外周血  miR-378a-3p  诊断价值
英文关键词: Acute coronary syndrome  Peripheral blood  miR-378a-3p  Diagnostic value
基金项目:国家自然科学基金(82070416)
作者单位邮编
张春生* 南京医科大学上海东方临床医学院 200120
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中文摘要:
      目的:探讨急性冠脉综合征(ACS)患者外周血miR-378a-3p的表达及其诊断价值。方法:收集ACS患者和健康人(control)血清各3份,进行基因芯片检测筛选发现miR-378a-3p差异表达最为显著。利用网络药理学分析miR-378a-3p与心肌缺血的相关性。构建小鼠心肌缺血再灌注(IR)模型,按缺血再灌注时间不同分为假手术(sham)组、I/R 1h组、I/R 3h组、I/R 6h组、I/R 12h组,检测外周血miR-378a-3p表达水平以及心肌肌钙蛋白T(cTnT)浓度水平。收集ACS患者(101例)和同期健康体检人群(49例),进行实时定量PCR,检测miR-378a-3p在ACS患者的表达。采用受试者工作特征曲线(ROC)分析miR-378a-3p诊断ACS的诊断效能,并对ACS进行风险评估。结果:基因芯片结果显示miR-378a-3p在ACS患者外周血中表达升高。网络药理学分析提示,miR-378a-3p与心肌缺血存在共同靶点且miR-378a-3p可能通过细胞凋亡和血管生成途径干预心肌缺血,有作为心肌缺血标志物的可能。动物实验证实miR-378a-3p表达量随心肌缺血时间变化逐渐上调且在6h时表达明显升高,且miR-378a-3p表达水平较cTnT更早在心肌缺血中出现高表达。临床数据分析表明,同健康对照组比较,ACS患者血清中的miR-378a-3p在发生ACS的临床症状后,在短时间内可以显著升高。miR-378a-3p作为ACS的特异性诊断指标时,曲线下面积(AUC)为0.8476(95%可信区间为0.7749- 0.9204,P<0.001),约登指数为0.6981,采用0.214作为cut-off值,miR-378a-3p诊断ACS的灵敏度和特异度分别为86.14%和83.76%。进一步的研究显示,在缺血的转化过程中,根据疾病分类的不同,结果显示miR-378a-3p的表达趋势也不同,在不稳定型心绞痛(UA)和心肌梗死(MI)组中,miR-378a-3p都显著上调(P<0.001),同MI患者相比,UA患者miR-378a-3p表达上调更显著(P<0.05),提示在诊断和判断ACS的分类中有较好的价值。结论:ACS患者外周血中miR-378a-3p表达升高是ACS发生的独立危险因素,早期检测miR-378a-3p有助于预测ACS的发病情况。
英文摘要:
      Objective:To investigate the expression of miR-378a-3p in peripheral blood of patients with acute coronary syndrome (ACS) and its diagnostic value.Methods:Three sera each from patients with acute coronary syndrome (ACS) and healthy individuals (control) were collected and screened by gene?microarray to find the most significant differential expression of miR-378a-3p.The correlation between miR-378a-3p and myocardial ischemia was analyzed using network pharmacology.A mouse myocardial ischemia reperfusion (IR) model was constructed and divided into sham operation, I/R 1h, I/R 3h, I/R 6h, and I/R 12h groups according to the time of ischemia and reperfusion, and the miR-378a-3p expression level in peripheral blood as well as the concentration level of cardiac muscle troponin T (cTnT) were detected. Patients with ACS (101 cases) and the same period of healthy physical examination population (49 cases) were collected and real-time quantitative PCR was performed to detect the expression of miR-378a-3p in patients with ACS. The diagnostic efficacy of miR-378a-3p for the diagnosis of ACS was analyzed by using the receiver operating characteristic curve(ROC) ,and the risk assessment of ACS was performed.Results:Gene microarray results showed that miR-378a-3p expression was elevated in the peripheral blood of patients with ACS. Network pharmacological analysis suggested that miR-378a-3p and myocardial ischemia share common targets and that miR-378a-3p may intervene in myocardial ischemia through apoptosis and angiogenic pathways,which may be used as a marker for myocardial ischemia.Animal experiments demonstrated that miR-378a-3p expression was gradually up-regulated with the duration of myocardial ischemia, and the expression was significantly increased at 6 h. Moreover, the expression level of miR-378a-3p appeared to be higher in myocardial ischemia at an earlier time than that of cTnT. Clinical data analysis showed that miR-378a-3p in the serum of patients with ACS could be significantly elevated within a short period of time after the clinical symptoms of ACS compared with healthy controls.When miR-378a-3p was used as a specific diagnostic indicator for ACS, the area under the curve (AUC) was 0.8476 (95% confidence interval 0.7749- 0.9204,P<0.001), the Yoden index was 0.6981, and the sensitivity and specificity of miR-378a-3p for diagnosing ACS were 0.214 adopted as the cut-off value, respectively were 86.14% and 83.76%.Further studies showed that during the transformation of ischemia, depending on the disease classification,the results showed different trends of miR-378a-3p expression.miR-378a-3p was significantly upregulated in both the unstable angina(UA) and myocardial infarction(MI) groups (P<0.001), and compared with MI, the upregulation of miR-378a-3p expression in peripheral blood of patients with UA was more significantly(P<0.05),suggesting a better value in diagnosis and judgment of ACS classification.Conclusion:Elevated miR-378a-3p expression in peripheral blood of patients with ACS is an independent risk factor for the development of ACS,and early detection of miR-378a-3p can help predict the development of ACS.
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