心房肌钙激活中性蛋白酶基因转录表达改变与心房颤动的关系

Alterations in gene expression of atrial calpains in patients with chronic atrial fibrillation

目的研究风湿性心脏瓣膜病（风心病）心房颤动（房颤）患者心房肌细胞钙激活中性蛋白酶（calpain1、calpain2）、钙激活中性蛋白酶（calpastatin）及L-型电压依赖钙通道alc亚基（LVDCCalc）的基因转录，探讨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calpain1、calpain2、calpastatin及LVDCCalc的mRNA表达水平。应用电镜观察房颤组与窦性心律组心房肌细胞超微结构。结果与窦性心律组相比，房颤组心房肌calpain1的mRNA表达水平上调（P〈0．05），LVDCCalc的mRNA表达水平显著下调（P〈0．01），且与calpainl的mRNA表达呈负相关（r=-0．583，P=0．019），而calpain2和calpastatin的mRNA表达水平差异无统计学意义（P〉0．05）；电镜结果显示房颤组心房肌细胞超微结构发生明显变化。结论房颤患者心房肌细胞calpain1和LVDCCalc的转录水平调控失衡，提示calpain1激活影响心肌细胞结构和通道蛋白水平，与房颤心房电重构和结构重构有关。

Objective To evaluate the molecular mechanisms involved in atrial calpains and L-type calcium channel alc subunit（ LVDCCalc） which occur in patients with atrial fibrillation （AF） and to investi-gate their effects on the initiation and maintenance of AF. Methods The right atrial appendages were obtained from 16 patients with atrial fibrillation （cases） and from 12 matched controls with sinus rhythm. The mRNA expression of proteins including ealpain1, calpain2 ,calpastatin and LVDCCal c was measured by semi-quantitative reverse transcription-polymerase chain reaction（RT-PCR） and normalized to the mRNA level of glyceraldehyde-3-phosphate dehydrogenase. Electron microscopy was applied to observe atrial muscle cell in tissue sample from fibrillating atria and normal atrium. Results Compared to sinus rhythm group, the mRNA level of calpainl was significantly increased （P〈0.05） , the mRNA level of LVDCCalc was significantly decreased in AF group （P〈0.01）. The mRNA level of LVDCCal c was negatively correlated with calpainl （r=-0.583,P=0.019）. No changes in the mRNA expression of calpain2 and calpastatin were observed between AF group and controls （P 〉0.05）. On electron microscopy, variation was apparent in the atrium myocyte uhramicrostructure in AF group. Conclusion Chronic AF is predominantly accompanied by abnormal regulation in the mRNA expression of calpainl and LVDCCalc, calpains may influence cadiocyte structure and channel protein level and are related to both electrical remolding and structural change.