摘要
目的:探讨卡托普利对慢性房颤(atrial fibrillation,AF)实验犬心房肌Ca2+调控蛋白基因表达的影响。方法:随机将26只健康杂种犬分为3组:对照组(6只)饲养8周,未作其他处置;起搏组(11只)及治疗组(9只)安置埋藏式高频率心脏起搏器(400bpm),快速起搏犬右心耳8周,治疗组于起搏前3d至起搏8周,每日给予卡托普利50mg2次/d。然后从右心房取材,测定心房肌细胞内Ca2+浓度,RTPCR方法检测细胞膜L型Ca2+通道及肌浆网钙泵(SRCa2+ATPase)mRNA表达。结果:8周后,对照组、起搏组、治疗组心房肌细胞内Ca2+浓度(μg·ml-1)分别为:24.06±3.51、35.32±4.88、25.44±4.19,起搏组细胞内Ca2+浓度明显增加(P<0.01);三组细胞膜L型Ca2+通道mRNA表达量分别为:0.27±0.03、0.20±0.03、0.33±0.04,起搏组mRNA表达量减少,而治疗组mRNA表达量明显增高,与对照组及起搏组比较P<0.05~0.001;三组SRCa2+ATPasemRNA表达量分别为:0.21±0.01、0.24±0.07、0.41±0.08,治疗组mRNA表达明显上调(P<0.001)。结论:实验犬快速起搏8周后,心房肌细胞内Ca2+超负荷,细胞膜L型Ca2+通道mRNA表达明显下调,SRCa2+ATPasemRNA表达无明显变化;卡托普利干预治疗可使细胞膜L型Ca2+通道及SRCa2+ATPasemRNA表达明显上调,从而抑制细胞内Ca2+超载。
Objective: To evaluate the effect of captopril on the gene expression of atrial calcium handling proteins in dogs with chronic atrial fibrillation. Methods: Twenty-six mongrel dogs were randomly divided into three groups. In control group all 6 dogs were fed for 8 weeks without any other treatment. In pacing group the permanent pacemakers (pacing at 400 bpm) were implanted in all 11 dogs to pace the right atrial appendage for 8 weeks. In treating group all 9 dogs were treated in the same way as to pacing group except that all dogs were given captopril 50 mg bid for 8 weeks. Samples were obtained from right atrial tissue at the end of the trial to determine the intracellular Ca^2+ concentration of atrial myocardium. The mRNA amounts of L-type calcium channel and sarcoplasmic reticulum (SR) calcium adenosine triphosphatase (Ca^2+ ATPase) were measured by RT-PCR. Results: At the end of the trial, the Ca^2+ concentration (μg.mlq)in control, pacing, and treating groups was 24.06±3.51, 35.32±4.88, and 25.44±4.19; mRNA level of L-type calcium channel 0.27±0.03, 0.20±0.03, and 0.33±0.04; mRNA level of SR Ca^2+-ATPase 0.21±0.01, 0.24±0.07, and 0.41±0.08 respectively. Conclusions: Long-term rapid atrial pacing may result in intracellular Ca^2+ overload and mRNA expression downregulation in L-type calcium channel in atrial myocardium, but the mRNA expression of SR Ca^2+-ATPase keeps unchanged. Captopril may significantly upregulate the mRNA expressions of L-type calcium channel and SR Ca^2+-ATPase, and therefore prevent the intracellular Ca^2+ overload in atrial myocardium.
出处
《山东大学学报(医学版)》
CAS
北大核心
2005年第10期889-892,共4页
Journal of Shandong University:Health Sciences
基金
国家自然科学基金资助项目(30370564)。