摘要目的：观察冠状动脉严重狭窄患者血浆中微小RNA-126（miR-126）水平与冠状动脉侧支循环（ CCC）形成的关系，探讨miR-126是否可成为CCC形成的生物标志物。方法本研究为前瞻性设计，连续入选2012年6月至2013年1月在北京安贞医院心内科接受选择性冠状动脉造影检查，证实左前降支、左回旋支或右冠状动脉中单支血管狭窄≥95％的冠心病患者（冠心病组），根据Rentrop分级将患者分成2个亚组：侧支良好亚组（Rentrop分级≥2）（n＝64），侧支不良亚组（Rentrop分级≤1）（n＝56）；另选取健康对照组30例。 RT-PCR检测血浆miR-126的表达水平，ELISA检测血清中血管内皮生长因子（ VEGF）的浓度。采用Pearson相关分析和多因素logistic回归进行相关性分析，采用受试者工作特征（ ROC）曲线分析血浆miR-126水平对CCC形成的辨别能力。结果侧支良好亚组的空腹血糖水平明显低于侧支不良亚组[（5.99±1.48）mmol/L 比（6.40±2.50）mmol/L，P＝0.044]。冠心病组血浆miR-126（0.04±0.01比0.07±0.02，P＝0.023）和血清VEGF水平[（2110±455）ng/L比（2574±450）ng/L，P＝0.011]均低于健康对照组。侧支良好亚组miR-126和VEGF水平明显高于侧支不良亚组[miR-126：0.06±0.02比0.03±0.01，P＝0.021；VEGF：（2549±614）ng/L比（1759±452）ng/L，P＝0.008]。侧支良好亚组血液中miR-126与VEGF呈正相关（r＝0.712，P＝0.005），侧支不良亚组miR-126与VEGF无相关性（r＝0.342，P＝0.483）。 logistic 回归分析显示， miR-126（OR＝2.145，95％CI 1.691～2.988，P＝0.001）和VEGF（OR＝1.279，95％CI 1.068～2.295， P＝0.013）是CCC形成的独立预测因子。以血浆miR-126水平为检验变量，ROC曲线分析显示曲线下面积为0.951（ P＝0.002）。结论血浆miR-126水平与CCC形成呈显著正相关，是CCC形成的独立预测因素，可能成为判别CCC形成情况的一种血液标志物。

abstractsObjective To explore the relationship between plasma microRNA 126 ( miR-126 ) level and coronary collateral circulation ( CCC) formation and to determine whether the miR-126 in plasma could serve as a blood-based biomarker for CCC in patients with severely narrowed coronary arteries ( CAD ).Methods In this prospective study , a total of 120 consecutive CAD patients with ≥95% stenosis in one epicardial coronary artery were enrolled.Thirty healthy people served as normal control.They were divided into two groups according to Rentrop grades:patients with grade 2 and 3 collateral development ( good CCC group, n=64) and patients with grade 0 and 1 collateral development (poor CCC group, n=56).Plasma miR-126 was measured by RT-PCR and serum VEGF was evaluated by ELISA method.Results Fasting plasma glucose ( FPG) was significantly lower in patients with good CCC than in patients with poor CCC ((5.99 ±1.48) mmol/L vs.(6.40 ±2.50) mmol/L).Plasma miR-126 levels and VEGF levels were significantly lower in CAD patients than in healthy people (0.04 ±0.01 vs.0.07 ±0.02, P=0.023 and (2 110 ±455) ng/L vs.(2 574 ±450) ng/L, P=0.011, respectively).miR-126 and VEGF levels were significantly higher in good CCC group than in poor CCC group ( miR-126:0.06 ±0.02 vs.0.03 ±0.01, P=0.021;VEGF:(2 549 ±614) ng/L vs.(1 759 ±452) ng/L, P=0.008).In CAD patients with good CCC, the miR-126 level was positively correlated to the VEGF expression (r =0.712,P=0.005) while there was no correlation between miR-126 level VEGF in CAD patients with poor CCC ( r =0.342, P =0.483).Multivariate analysis revealed that plasma miR-126 ( OR=2.145,95%CI 1.691 -2.988, P =0.001) and VEGF ( OR =1.279, 95%CI 1.068 -2.295, P =0.013 ) were independent predictors of collateral formation in patients with severely narrowed coronary arteries.In CAD patients , the area under the miR-126 ROC curve is 0.951 ( P=0.002).Conclusion Plasma miR-126 level is positively correlated to the CCC formation and is an independent predictor of CCC development in patients with severely narrowed coronary arteries , suggesting that plasma miR-126 might be a useful new , stable blood biomarker for predicting CCC formation in patients with severely narrowed coronary arteries.