心房颤动电重构心房肌Ca^(2+)调控蛋白异常与解剖学改变关系的研究

Alterations in gene expression of calcium handling proteins and atrial structural change in patient with chronic atrial fibrillation

目的 探讨心房肌Ca2 + 调控蛋白 (calciumhandlingproteins)在心房颤动 (atrialfibrillation ,AF)电重构中的作用及与解剖学结构改变的关系。方法 测定 10例慢性AF患者和 6例对照组心房肌Ca2 + 含量和细胞膜L型Ca2 + 通道 (L typecalciumchannel)、肌浆网钙泵 (sarcoplasmicreticulumcalciumadenodinetriphosphatase ,SRCa2 + ATPase)、磷酸受纳蛋白 (phospholamban)、兰尼碱受体 (ryanodinere ceptor)和肌集钙蛋白 (calsequestrin)的信使核糖核酸 (messengerribonucleicacid ,mRNA)表达 ;测量AF患者左、右心房内径、二尖瓣口面积和肺动脉收缩压。结果 与对照组比较 ,AF患者心肌细胞内Ca2 +含量增加 [(1330± 770 ) μg/mlvs(30 2± 31) μg/ml,P <0 0 1];细胞膜L型Ca2 + 通道、SRCa2 + ATPase和兰尼碱受体mRNA下调 [(0 6 5± 0 30 )vs(0 97± 0 19) ,P <0 0 1;(0 73± 0 13)vs(1 10± 0 11) ,P<0 0 0 1;(0 71± 0 2 5 )vs(0 90± 0 13) ,P <0 0 5 ]。SRCa2 + ATPasemRNA表达与左心房内径中度负相关 (r=- 0 .5 6 ,P <0 .0 5 ) ;与二尖瓣口面积正相关 (r =0 .70 ,P <0 .0 5 ) ;细胞膜L型Ca2 + 通道mR NA表达与二尖瓣口面积显著正相关 (r =0 .84,P <0 .0 1)。

Objective To evaluate the mRNA expression of calcium handling proteins and relationship between the alteration in gene expression and atrial structural change in patients with persistent atrial fibrillation (AF).Methods Left atrial tissues were obtained from 10 patients with chronic AF(>12 months) and 6 brain death subjects with normal heart.The underlying heart disease was rheumatic mitral valvular stenosis.The Ca 2+ concentration of the atrial 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 was measured by RT-PCR.The left atrial diameter (LAd),mitral valvular area (MVA) and systolic pulmonary arterial pressure were obtained by echocardiography before surgery.Results Compared with control subjects,the Ca 2+ concentration was significantly increased [(1 330±770)μg/ml vs(301±30)μg/ml, P <0.01)].The mRNA levels of L-type calcium channel,SR Ca 2+ -ATPase and RyR were significantly decreased [(0.65±0.30)vs(0.97±0.19), P <0.01;(0.73±0.13)vs(1.10±0.11), P <0.001;(0.71±0.25)vs(0.90±0.13), P <0.05)].Correlations were found between MVA and mRNA levels of L-type calcium channel,SR Ca 2+ -ATPase ( r =0.84, P <0.01; r =0.70, P <0.05).The mRNA levels of L-type calcium channel was negatively correlated with LAd( r =-0.56, P <0.05).Conclusion Our results provide the evidence of abnormalities of intracellular Ca 2+ homeostasis in patients with chronic AF.Down regulation in mRNA expressions of L-type calcium channel,SR Ca 2+ -ATPase,and Ry R may be the molecular mechanism of intracellular Ca 2+ overload.The correlation between altered gene expression of gene expression of Ca 2+ handling protein and LAd,MVA suggests that the progressive nature of AF involves a continuum of electrophysiological and structural changes.