慢性心房颤动患者心房肌钙转运调控蛋白基因转录表达的改变

Alterations in Gene Expression of Calcium Handling Proteins in Patients with Chronic Atrial Fibrillation

目的探讨心房颤动(AF)时心房肌细胞钙超载的原因及其在AF发生和维持中的作用。方法采集风湿性心脏瓣膜病窦性心律患者12例(对照组)和AF患者14例(AF组)的右心耳组织,采用RT-PCR方法检测心房肌钙转运调控蛋白mRNA表达水平,测量AF患者左右心房内径、二尖瓣口面积和肺动脉收缩压。结果与对照组相比,AF组患者L-型电压依赖钙通道a1c亚基(LVDCCa1c)、肌浆网Ca2+-ATP酶和兰尼碱受体(RYR2)的mRNA表达水平显著下调(P均<0.01),三磷酸肌醇受体(IP3R1)的mRNA表达水平上调(P<0.05),而磷酸受纳蛋白和肌集钙蛋白的mRNA表达水平无明显改变(P均>0.05)。AF组患者肌浆网Ca2+-ATP酶的mRNA表达水平与左心房内径呈负相关(r=-0.573,P=0.032),与二尖瓣口面积呈正相关(r=0.625,P=0.017);LVDCCa1c的mRNA表达水平与二尖瓣口面积呈正相关(r=0.719,P=0.004)。结论细胞内钙超载机制可能参与了AF的发生和维持,心房肌钙转运调控蛋白mRNA表达异常可能是钙超载的分子生物学机制,钙转运调控蛋白mRNA表达异常与左心房解剖学改变之间存在内在联系。

Objective To discuss the role of calcium-overloading in initiation and maintenance of atrial fibrillation （AF）. Methods The right atrial appendages were obtained from 14 patients with AF and 12 patients with sinus rhythm. The mRNA expression of proteins influencing the calcium homeostasis was measured by semi-quantitative reverse transcription-polymerase chain reaction （RT-PCR） and normalized to the mRNA level of glyceraldehyde-3- phosphate dehydrogenase. The left atrial diameter （LAD）, mitral valvular area （MVOA） , and systolic pulmonary arterial pressure were obtained by echocardiography before surgery. Results Compared to sinus rhythm group, the mRNA levels of L-type calcium channel al c, sarcoplasmic reticulum （ SR）, calcium adenosine triphosphatase （ Ca^2＋ -ATPase）, and ryanodine receptor type-2 （ RYR2 ） were significantly decreased （ P 〈 0. 01 ） ; the mRNA level of inositol triphosphate receptor type-1 （ IP3R1 ） was significantly increased （ P 〈 0. 05 ）. No changes in the mRNA expression of phospholamban and calsequestrin were observed between two groups （ P 〉 0. 05 ）. Correlations were found between MVOA and mRNA levels of LVDC-Cale, SR Ca^2＋-ATPase （r=0.719, P=0.004; r=0.625, P=0.017）. The mRNA level of SR Ca^2＋- ATPase was negatively correlated with LAD （ r = - 0. 573, P = 0. 032）. Conclusions Calcium loading may be responsible for the occurrence and maintenance of AF, and abnormal regulation in the mRNA expression may be the molecular mechanism of intracellular Ca^2＋ overload. The progressive nature of AF involves structural change.