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目的观察miR-126在冠状动脉支架内再狭窄(ISR)患者外周血中的表达并评估其意义。方法收集2014年6月至2015年12月在济宁医学院附属医院心内科住院的26例支架内再狭窄患者为ISR组,收集同期未发生支架内再狭窄的患者40例,为non-ISR组。分别观察各组的临床资料和冠脉支架手术资料,用实时荧光定量聚合酶链反应(Real-time PCR)检测miR-126表达,比较两组间的miR-126表达差异;通过ROC曲线评估miR-126对冠脉支架术后患者发生ISR的诊断价值。生物信息学预测miR-126的靶基因,并对这些靶基因进行功能分析和富集。结果ISR组与non-ISR组在冠脉病变特点和手术特点比较:支架直径[(3.21±0.88)mm,(3.15±0.67)mm]、支架长度[(20.83±4.92)mm,(21.02±4.75)mm]、支架释放最大压力[(14.17±9.1)atm,(13.97±6.26)atm]两组间均差异无统计学意义(t=0.97,-1.04,0.87;P>0.05)。miR-126在ISR组中的表达量(0.63±0.38)低于non-ISR组(1.36±1.03),差异有统计学意义(t=-5.46,P<0.01)。ROC曲线分析基线miR-126对冠脉支架术后患者12~18个月时发生ISR的曲线下面积(AUC)为0.791(95%CI 0.671~0.912,P<0.01)。通过数据库预测出miR-126的靶基因,对这些靶基因进行基因功能富集,发现其主要作用方向是:血管内皮生长因子信号通路、细胞外基质、细胞增殖调节等。结论miR-126下降的冠脉支架患者在术后随访期间发生ISR的危险度增加,miR-126是冠脉支架患者发生ISR的预测因素。miR-126的生物功能主要集中于血管内皮生长因子信号通路方向,这可能是其参与ISR过程的一个途径。
Objective To observe the expression of miR-126 in peripheral blood of patients with coronary stent restenosis (ISR) and to evaluate its significance. Methods Twenty-six patients with in-stent restenosis who were hospitalized in Department of Cardiology, Affiliated Jining Medical College from June 2014 to December 2015 were enrolled in ISR group. Forty patients with no in-stent restenosis during the same period were enrolled as non-ISR group . The clinical data of each group and the data of coronary stenting were observed. Real-time PCR was used to detect the expression of miR-126, and the differences of miR-126 expression between the two groups were compared. The ROC curve was used to evaluate the expression of miR -126 in the diagnosis of coronary artery disease in patients with ISR diagnosis. Bioinformatics predicts the target genes of miR-126 and performs functional analysis and enrichment of these target genes. Results The characteristics of coronary lesions and surgical characteristics of ISR group and non-ISR group were as follows: diameter of stent (3.21 ± 0.88 mm, (3.15 ± 0.67) mm, length of stent (20.83 ± 4.92 mm, (21.02 ± 4.75 ) mm]. There was no significant difference between the two groups (t = 0.97, -1.04, 0.87; P> 0.05). The expression of miR-126 in ISR group (0.63 ± 0.38) was lower than that in non-ISR group (1.36 ± 1.03), the difference was statistically significant (t = -5.46, P <0.01). ROC Curve Analysis The area under the curve (AUC) for ISR occurred at 12 to 18 months after coronary stenting in baseline miR-126 patients was 0.791 (95% CI 0.671 to 0.912, P <0.01). The target genes of miR-126 were predicted from the database, and the gene function enrichment of these target genes was found. The main directions of action are: vascular endothelial growth factor signaling pathway, extracellular matrix, cell proliferation regulation and the like. Conclusions Patients with coronary stents with decreased miR-126 have an increased risk of ISR during follow-up, and miR-126 is a predictor of ISR in patients with coronary stents. The biological function of miR-126 mainly focused on the direction of vascular endothelial growth factor signaling, which may be one of the ways of its involvement in ISR.