大鼠心肌梗死转SERCA2a基因对心脏电生理影响的研究
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摘要
目的:转SERCA2a基因治疗对心衰的改善已经取得了一致的认可,但对心律失常转归的影响存在争议。本研究用三种电生理方法观察大鼠心梗转SERCA2a基因后存活心肌电生理的变化,以明确转SERCA2a基因对心梗后心肌电活动的影响。方法:50只雄性SD大鼠,随机平均分为盐水组与SERCA组,结扎左冠状动脉前降支,建立大鼠心梗模型;采用局部多点注射法分别向两组大鼠心梗周围区注入盐水与SERCA2a基因;记录结扎冠脉前、结扎即刻及干预两周后心电图,观察R-R间期、QRS间期、QT间期及心律失常发生率的变化;双极电位标测法观察干预两周后心肌局部电位时程的变化;MEA观察干预两周后心肌组织间场电位时程(FPd)变化;分别在术前、术后一周、术后两周行超声心动图检测,观察心功能变化。结果:模型成活率为60 %,术后两周盐水组大鼠存活10只,SERCA组大鼠存活15只;结扎即刻、盐水组术后两周、SERCA组室术后两周室性心律失常发生率分别为36%、30%与0,与术前相比,盐水组术后两周QT间期延长、RR间期延长,而SERCA组QRS时程缩短、QT间期缩短(P<0.05);盐水组梗死周围区局部电位时程长于对侧区,而SERCA组结果相反,SERCA组局部电位时程离散度小于盐水组(P<0.05);两组梗死周围区场电位时程较梗死对侧区均缩短(P<0.05),但SERCA组场电位离散度显著小于盐水组(P<0.05);心超显示术后一周两组EF、FS值均有所下降,术后两周时盐水组指标持续下降,而SERCA组EF、FS值明显回升(P<0.05)。结论:转SERCA2a基因,有预防心梗后心律失常发生、改善心功能、防止心室重构的作用。MEA技术,是观察心梗后存活组织电活动一致性的理想工具。
Objective:To study the therapy effect of adenoviral gene transfer of SERCA2a on cardiac electrophysiology 2 weeks after acute myocardial infarction(AMI) and the possible mechanism of the therapy effect. Methods:50 SD rats were divided into saline group and SERCA group; AMI rats were obtained by ligating left anterior descending coronary artery; 0.9% sodium chloride solution and recombinant adenovirus carrying SERCA2a gene were respectively delived to the heart of AMI rats in two groups by directed injection around the ischemic area; electrocardiograph were tested during the surgery and two weeks after the surgery, the QRS interval, R-R interval, QT interval and arrhymic incidence rate were ananlyzed; local potential and field potential were detected by dipolar potential test and MEA two weeks after transgene; echocardiogram were tested before surgery, one weeks and two weeks after surgery. Results:The survivle rate of the model rats is 60%; arrhythmic incidence rate in control group, saline group and SERCA2a group are 36%, 30% and 0; compare to the contol group, QT interval and R-R interval are prolongated in saline group, but QT interval and QRS interval are shortened in SERCA group(P<0.05); two weeks after gene transfer, the dispersion of the local potentail and field potential duration is longer in saline group than it in SERCA group (P<0.05); one week after transgene, EF and FS are dcreased in both two groups, one more week later, EF and FS continued decreasing in saline group, but they increased in SERCA group. Conclusions:Adenoviral gene transfer of SERCA2a can reduce the incidence of arrhythmia and improve the heart function after AMI in rats; MEA is a ideal method to study the concordence of the myocardia in different part of whole heart.
Objective:To study the therapy effect of adenoviral gene transfer of SERCA2a on cardiac electrophysiology 2 weeks after acute myocardial infarction(AMI) and the possible mechanism of the therapy effect. Methods:50 SD rats were divided into saline group and SERCA group; AMI rats were obtained by ligating left anterior descending coronary artery; 0.9% sodium chloride solution and recombinant adenovirus carrying SERCA2a gene were respectively delived to the heart of AMI rats in two groups by directed injection around the ischemic area; electrocardiograph were tested during the surgery and two weeks after the surgery, the QRS interval, R-R interval, QT interval and arrhymic incidence rate were ananlyzed; local potential and field potential were detected by dipolar potential test and MEA two weeks after transgene; echocardiogram were tested before surgery, one weeks and two weeks after surgery. Results:The survivle rate of the model rats is 60%; arrhythmic incidence rate in control group, saline group and SERCA2a group are 36%, 30% and 0; compare to the contol group, QT interval and R-R interval are prolongated in saline group, but QT interval and QRS interval are shortened in SERCA group(P<0.05); two weeks after gene transfer, the dispersion of the local potentail and field potential duration is longer in saline group than it in SERCA group (P<0.05); one week after transgene, EF and FS are dcreased in both two groups, one more week later, EF and FS continued decreasing in saline group, but they increased in SERCA group. Conclusions:Adenoviral gene transfer of SERCA2a can reduce the incidence of arrhythmia and improve the heart function after AMI in rats; MEA is a ideal method to study the concordence of the myocardia in different part of whole heart.
引文
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[6] Sarah Fernandes, Jean-Christophe Amirault, Gilles Lande, etal. Autologous myoblast transplantation after myocardial infarction increases the inducibility of ventricular arrhythmias[J]. Cardiovascular Research, 2006, 69: 348-358
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[14]陈颖,刘艳,J J Mercadier.肌浆网钙ATP酶高表达对大鼠心肌梗死的影响[J].国际心血管病杂志,2006,33(4):278-281
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