microRNA-155在慢性心房颤动心房3型小电导钙激活钾通道重构中的作用

The role of microRNA-155 in remodeling of small conductance calcium activated potassium channel 3 in human chronic atrial fibrillation

目的:初步探讨microRNA-155(miR-155)在慢性心房颤动(房颤)中3型小电导钙激活钾通道(SK3)重构中的作用。方法:将67例心脏瓣膜病外科手术患者分为房颤组(31例)和窦律组(36例),利用实时荧光定量PCR分别检测两组患者右心耳miR-155与SK3mRNA表达水平,免疫印迹法检测SK3蛋白表达水平;分别利用miR-155mimic和miR-155inhibitor干预人心肌细胞系(AC16细胞系),观察其对AC16细胞SK3mRNA和蛋白表达水平的影响。结果:房颤组右心耳miR-155表达水平较窦律组显著上调(1.292±0.261︰0.310±0.161,P<0.01)。房颤组右心耳SK3mRNA表达水平与窦律组无显著差异(0.855±0.295︰0.917±0.253,P>0.05),但房颤组右心耳SK3蛋白表达水平较窦律组显著下调(0.182±0.043︰0.302±0.064,P<0.01)。两组患者右心耳miR-155表达水平与SK3蛋白表达水平呈负相关(r=-0.735,P<0.01)。miR-155 mimic减少AC16细胞SK3蛋白表达,而miR-155inhibitor则增加SK3蛋白表达,但两者均对SK3mRNA的表达无影响。结论:慢性房颤患者右心房miR-155表达上调,可能通过下调SK3表达水平,参与房颤的发生与维持。

Objective：To investigate the effect of microRNA-155（miR-155）on remodeling of small conductance calcium activated potassium channel 3（SK3）in human chronic atrial fibrillation（AF）.Method：Right atrial appendages were obtained from 67 patients undergoing cardiac surgery,including 31 patients with chronic AF and36 patients with sinus rhythem（SR）.The expression level of miR-155 was determined by real-time quantitative PCR.The mRNA or protein levels of SK3 were determined by real-time quantitative PCR Western blot,respectively.miR-155 mimic and miR-155 inhibitor were transfected into AC16 cells,respectively.Result：The expression of miR-155 was found to be significantly up-regulated in AF patients compared with patients with SR（1.292±0.261 vs 0.310±0.161,P0.01）.No significant difference at the mRNA expression level of SK3 was found between patients with AF and patients with SR（0.855±0.295 vs 0.917±0.253,P0.05）,but the protein expression of SK3 in patients with AF was significantly lower than that of patients with SR（0.182±0.043 vs 0.302±0.064,P0.01）.There was a negative correlation between the expression level of miR-155 and the protein expression level of SK3 in right atrial appendage（r=-0.735,P0.01）.miR-155 mimic reduced the protein expression of SK3 in AC16cells,while miR-155 inhibitor increased the protein expression of SK3,but both had no effect on the mRNA expression of SK3.Conclusion：Upregulation of miR-155 may contribute to atrial electrical remodeling in human atrial fibrillation by targeting SK3.