糖尿病合并冠心病患者血清标志物miR-24的变化及临床意义
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(西南医科大学1.药物研究中心,;2.临床医学,;3.心血管药理系,四川省泸州市 646000)

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方丹,硕士研究生,讲师,研究方向为糖尿病周围血管病变,E-mail为fangdan198301@163.com。

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国家自然科学基金项目(81172050、81570263);国家级大学生创新创业训练计划项目(201710632043);四川省教育厅重点项目(16ZA0178);泸州市科技局项目(2017LZXNYD-T05、2016LZXNYD-J24、2016-R-70(11/24、8/24))资助


Altered levels and clinical significance of serum miR-24 as a potential biomarker in diabetes mellitus with coronary heart disease
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1.Drug Discovery Research Center, ;2.Department of Clinical Medicine, ;3.Department of Cardiovascular Pharmacology, Southwest Medical University, Luzhou, Sichuan 646000, China)

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    摘要:

    目的 深入调查糖尿病合并冠心病患者血清miR-24及其靶标YKL-40的变化及作用机制,探讨血清miR-24作为糖尿病合并冠心病潜在分子标志物的临床意义。方法 收集行冠状动脉造影术确诊的患者61例,并根据冠状动脉造影结果及糖尿病诊断标准分为单纯冠心病组(CHD)、糖尿病合并冠心病组(DM+CHD),并且同期选取32例冠状动脉造影阴性的人群作为对照组。Gensini积分方法评价冠状动脉病变程度;qRT-PCR检测血清miR-24及靶标YKL-40 mRNA变化;ELISA检测血清YKL-40蛋白水平;受试者工作特征(ROC)曲线评估血清miR-24对糖尿病合并冠心病的诊断效率。结果 miR-24在DM+CHD组患者血清中水平显著低于对照组和单纯CHD组,并且单纯CHD组血清miR-24水平也显著低于对照组。相对的,DM+CHD组患者血清YKL-40 mRNA和蛋白水平则显著高于对照组和单纯CHD组,同时单纯CHD组也显著高于对照组。ROC曲线分析结果显示,血清miR-24水平对区分DM+CHD和非DM+CHD以及DM+CHD和CHD患者均具备较高诊断价值,ROC曲线下面积(AUC)及其95%CI分别为0.919(95% CI:0.856~0.983)和0.901(95% CI:0.814~0.988)。结论 糖尿病合并冠心病患者血清miR-24呈下调变化趋势并且具有较高DM+CHD诊断价值,提示血清miR-24是潜在的糖尿病合并冠心病患者临床早期诊断标志物。

    Abstract:

    Aim To investigate the changes of serum miR-24 and its target gene YKL-40 in diabetes mellitus (DM) with coronary heart disease (CHD) and explore its clinical significance as a predictive potential biomarker. Methods According to the coronary arteries angiography and diabetes diagnostic criteria, the study included 61 subjects with CHD subjects (n=34), DM+CHD subjects (n=27), and 32 negative predictive value of coronary angiography (control) in our affiliated hospital from October 2013 to June 2016. Gensini score was used to evaluate the severity of coronary artery lesions. Bioinformatic analysis and identification of serum miR-24 and its target YKL-40 were assessed using quantitative real-time PCR, ELISA after a bicinchoninic acid (BCA) assay, and receiver-operating characteristic (ROC) assays. Results miR-24 was especially gradually decreased in serum of CHD and DM+CHD patients compared with controls and reached to minimum in DM+CHD groups, and conversely, its target YKL-40 mRNA and protein levels were significantly increased in serum of CHD and DM+CHD patients and reached to maximum in DM+CHD groups. Furthermore, the area under the curve (AUC) and 95% confidence interval (CI) for the receiver-operating characteristic (ROC) analysis was 0.919 (95% CI:0.856~0.983) and 0.901 (95%CI:0.814~0.988), suggesting that the levels of miR-24 have high diagnostic values in distinguishing between DM+CHD and non-DM+CHD, or DM+CHD and CHD. Conclusions Serum circulating miR-24 was significantly decreased in patients with DM+CHD that had high clinical diagnostic value, indicating that miR-24 could be a potential biomarker for predicting diabetes mellitus with coronary heart disease.

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方丹,邓鑫,贺朝晖,吴剑波,罗茂.糖尿病合并冠心病患者血清标志物miR-24的变化及临床意义[J].中国动脉硬化杂志,2018,26(5):491~496.

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  • 收稿日期:2017-09-01
  • 最后修改日期:2017-10-10
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  • 在线发布日期: 2018-05-31