心房颤动患者心房肌Ca^(2+)调控蛋白基因的表达变化

Gene expression of calcium handling proteins in patients with persistent atrial fibrillation

目的:探讨心房肌细胞内Ca2+超负荷及Ca2+调控蛋白在心房颤动(AF)时心房肌电重构中的作用。方法:测定10例慢性AF患者和6例对照组心房肌细胞内Ca2+含量和细胞膜L型Ca2+通道、肌浆网钙泵、磷酸受纳蛋白、兰尼硷受体和肌集钙蛋白的mRNA和蛋白质表达。结果:与对照组比较,AF患者心房肌细胞内Ca2+含量提高4.4倍;细胞膜L型Ca2+通道mRNA表达下调33%;肌浆网钙泵mRNA和蛋白质表达分别减低34%和27%;兰尼硷受体mRNA下调21%(P<0.05～0.001);磷酸受纳蛋白mRNA和蛋白质表达及肌集钙蛋白的mRNA表达差异无统计学意义(P>0.05)。结论:频率相关的细胞内Ca2+超负荷可能是AF电重构的始动因素,心房肌Ca2+调控蛋白异常是Ca2+超负荷的分子生物学机制,在AF的发生和发展中起重要作用。

Objective:To evaluate the mRNA and protein expression of calcium handling pro-teins in patients with persistent atrial fibrillation(AF).Methods:Left atrial tissues were obtained from10patients of rheumatic mitral valvular stenosis with persistent AF (>12months)and6brain death subjects with normal heart.The Ca 2+ concentration of the artial myocardium was measured.The mRNA amount of L-type calcium channel and sarcoplasmic reticulum(SR)calcium adenosine triphosphatase(Ca 2+ -ATPase),phospholamban,ryanodine receptor(RyR),calsequestrin were measured by RT-PCR.Western blot analysis was performed to study protein expression of SR Ca 2+ -ATPase and phospholamban.Results:In the comparative study in the AF paients,the Ca 2+ concentration was significantly increased(1330±770μg/ml vs301±30μg /ml,P<0.01),the mRNA levels of L-type calcium channel and SR Ca 2+ -ATPase,RyR were significantly decreased(0.65±0.30vs0.97±0.19,P<0.01;0.73±0.13vs1.10±0.11,P<0.001;0.71±0.25vs0.90±0.13,P<0.05)and protein level of SR Ca 2+ -ATPase was reduced(0.74±0.07vs1.02±0.4,P<0.05).Con clusion:The results suggest that intracellular calcium overload plays an impor-tant role in atrial electrical remodeling.Down regulation in mRNA and protein expressions of L-type calcium channel and SR Ca 2+ -ATPase,RyR may be the molecular mechanism of intracellular Ca 2+ over-load.