心脏瓣膜病心房颤动患者左心房HCN通道及5-HT4一R表达的研究

The expression of atrial hyperpolarizationactivated cyclic nucleotidegated channel and 5hydroxytryptamine4receptor in valvular heart disease patients with atrial fibrillation

目的研究心脏瓣膜病心房颤动（房颤）患者左心房肌超极化激活环化核苷酸门控通道（HCN）各亚型及其调节受体5一羟色胺4受体（5-HT4一R）基因表达及蛋白表达。方法86例心脏瓣膜置换术后患者，窦性心律38例，房颤48例，术中取左心耳组织，用实时定量聚合酶链反应（pcR）和蛋白免疫印记法（westernblot）的方法测定HCN通道各亚型及5-HT4．R基因表达和蛋白表达。结果同窦性心律组相比，房颤组患者心房肌HCN2、HCN4的mRNA表达及蛋白表达水平上调，5-HT4-RmRNA表达及蛋白表达水平下调，HCNl的mRNA表达及蛋白表达在房颤组患者中亦有增高，但差异无统计学意义。HCN2的mRNA表达及蛋白表达与左心房内径呈正相关。5-HT4-RmRNA表达水平下调与左心房内径呈负相关。结论左心房肌HCN2、HCN4的mRNA表达及蛋白表达上调及5-HT4．RmRNA表达及蛋白表达水平下调可能是瓣膜病房颤患者左心房肌电重构的分子基础之一。

To evaluate the gene expression and protein expression of atrial hyperpolarizationactivated cyclic nucleotidegated channel （HCN） informs and 5hydroxytryptamine4 receptor gene expression in valvular heart disease patients with atrial fibrillation（AF）. Methods Left atrial tissue were obtained from 86 patients with valvular heart disease who underwent cardiac valve replacement. Thirtyeight patients were in sinus rhythm ,48patients were in chronic atrial fibrillation. The mRNA level of HCN and HT4-R and protein expression were measured by realtime quantitative polymerase chain reaction （ Realtime PCR） and western blot. Results Compared to sinus rhythm group, the mRNA level of HCN2 and HCN4 were increased in AF group. But 5-HTa-R was versa. The mRNA and protein expression of HCN1 was slightly higher in AF group,but the differences were not statistically significant. The mRNA of HCN2 was significantly positive correlated with left atrial dimension. The mRNA of 5-HT4-R was negtive correlated with the left atrial dimension. Conclusion The increase of mRNA and protein expression level of HCN2 and HCN4 may be a very important molecular mechanism in patients with AF,involving electrical remodeling.