| 张春生,焦甜甜,许铃浩,王 亮,程 静,李纪明.急性冠脉综合征患者外周血miR-378a-3p的表达及其诊断价值[J].,2024,(11):2104-2110 |
| 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：2024-02-08 修订日期：2024-02-26 |
| DOI：10.13241/j.cnki.pmb.2024.11.019 |
| 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:国家自然科学基金项目（82070416） |
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| 中文摘要: |
| 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: |
| ABSTRACT 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 1 h, I/R 3 h, I/R 6 h, and I/R 12 h 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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