风湿性心脏病慢性心房颤动患者钙转运调控蛋白和钙激活中性蛋白酶基因转录的表达改变

Alterations in gene expression of calcium handling proteins and atrial calpains in chronic atrial fibrillation patients with rheumatic heart disease

目的测定心房肌钙转运调控蛋白和钙激活中性蛋白酶(calpain1)的mRNA表达,探讨风湿性心脏瓣膜病(风心病)心房颤动(房颤)患者心房肌电重构和结构重构以及心功能下降的分子生物学机制及其在房颤发生、维持中的作用。方法采集风心病窦性心律组患者12例和房颤组患者16例的右心耳组织,应用半定量逆转录-聚合酶链反应(RT-PCR)方法,测定心房肌钙转运调控蛋白和calpain1的mRNA表达水平。结果与窦性心律组相比,房颤组L-型电压依赖钙通道a1c亚基(LVDCCa1c)、肌浆网Ca2+-ATP酶、兰尼碱受体(RYR2)的mRNA表达水平明显下调(均为P<0.01),三磷酸肌醇受体(IP3R1)的mRNA表达水平上调(P<0.05),房颤组心房肌calpain1的mRNA表达水平上调(P<0.05),且与LVDCCa1c的mRNA表达呈负相关(r=-0.583,P<0.05)。结论房颤患者心房肌钙转运调控蛋白和calpain1转录水平调控失衡可能是心房肌电重构和结构重构以及心功能下降的分子生物学机制之一,与房颤的发生和维持有关。

Objective To investigate the molecular mechanisms of chronic atrial fibrillation （AF） by assessing gene expression of calcium handling proteins and atrial calpains in AF patients. Methods A hundred microgram of tissue of right atrial appendages was obtained from 16 rheumatic heart disease patients with AF and 12 matched rheumatic heart disease patients with sinus rhythm （as control） during cardiac operation. The mRNA expression of calcium handling proteins and atrial calpains were assessed by semi-quantitative reverse transcription-polymerase chain reaction （RT-PCR） and normalized to the mRNA level of glyceraldehyde-3-phosphate dehydrogenase. Results mRNA level of calpainl was significantly increased （P〈 0. 05） and mRNA level of LVDCCalc was significantly decreased （P〈0.01） in AF group than in sinus rhythm group, mRNA level of LVDCCalc was negatively correlated to that of calpainl（r=-0. 583,P〈0.05 ）. Compared to sinus rhythm group, AF group had significantly decreased levels of sarcoplasmic reticulum（SR） calcium adenosine triphosphatase （Ca2＋-ATPase） and ryanodine receptor type-2mRNA （P〈0. 01 ） and significantly increased level of inositol triphosphate receptor typelmRNA （P〈0.05）. Conclusions Chronic AF is predominantly accompanied by abnormal regulation in the mRNA expression of proteins influencing the calcium homeostasis and atrial calpain1, which are related to both electrical remodeling and structural change and may influence the initiation and maintenance of AF.