微小RNA-21/JAG1通路在比格犬房颤模型中的作用及其机制

Mechanism of microRNA-21/JAG1 pathway in chronic atrial fibrillation Beagle model induced by right atrial appendix tachy-pacing

目的探讨微小RNA(miRNA,miR)-21/JAG1通路在房颤(AF)中的作用及其机制.方法36条比格犬随机分为6组,每组6条,分别为对照组、单纯起搏组、抑制miR-21表达组、抑制miR-21表达阴性病毒组、miR-21过表达组、miR-21过表达阴性病毒组.病毒组于右心耳组织内多点注射腺相关病毒,其中除对照组外其余各组术后1周开始右心耳起搏器快速起搏.起搏6周后进行AF易感性和超声心动图检测,右心耳组织形态学观察,蛋白质印迹法(Western blot)检测JAG1和胶原蛋白-1(Collegen-1).应用IBM SPSS Statistics version 22.0统计软件分析.计量数据统计应用t检验,分类数据统计使用x2检验.结果纯起搏组AF发生率为66.7%,心律失常率为100%,其与对照组比较,差异有统计学意义(P<0.01).miR-21过表达组的AF(83.3%)和心律失常(100%)发生率最高;miR-21过表达阴性病毒组AF发生率为66.7%,无其他心律失常发生.两组在AF和心律失常发病率比较差异无统计学意义(P>0.05),但前者有升高趋势.同样,miR-21过表达组的左房直径有扩大趋势[(25.7±2.1)mm比(23.6±0.6)mm].Collegen-1和JAG1蛋白表达量在两组表达差异有统计学意义(t=2.636,P<0.05;t=-2.456,P<0.05).Collegen-1在miR-21过表达组中表达明显上调,而JAG1的蛋白表达明显降低.上述检测值在其他组间差异均无统计学意义(P>0.05).结论miR-21/JAG1通路可能促进心房纤维化和AF的形成.

Objective To explore the function of microRNA(miRNA,miR)-21/JAG1 pathway in atrial fibrillation(AF).Methods Thirty-six canines were randomly divided into 6 groups:control group,tachy-pacing group,miR-21 inhibition group,miR-21 inhibition negative virus group,miR-21 mimic group,and miR-21 mimic negative virus group.Multi-point injection of adeno-associated virus in right atrial appendage tissue was implemented in virus groups.The right atrial pacemaker rapid pacing was started in all groups except the control group one week after operation.The incidence of atrial fibrillation and echocardiography,the histomorphology of the right atrial were observed after 6 weeks of pacing.JAG1 and Collegen-1(ColⅠ)were detected by Western blotting.Results The incidence of AF(83.3%)and arrhythmia(100%)was the highest in the miR-21 mimic group,the incidence of AF was 66.7%in the miR-21 mimic negative virus group.There was no significant difference in the incidence of atrial fibrillation and arrhythmia between the two groups,but the former tended to increase.Similarly,the diameter of the left atrium showed an enlargement trend[(25.7±2.1)mm vs.(23.6±0.6)mm]in the miR-21 mimic negative virus group.The expression levels of ColⅠand JAG1 protein were significantly different between the two groups(t=2.636,P<0.05;t=-2.456,P<0.05).ColⅠwas up-regulated in the over-expression group of microRNA-21,while JAG1 was down-regulated.There was no statistical difference between the other groups(P>0.05).Conclusion The miR-21/JAG1 pathway may promote the formation of atrial fibrosis and atrial fibrillation.