摘要
目的研究依那普利、厄贝沙坦及血管紧张素-(1-7)[Ang-(1-7)]对快速心房起搏犬心房肌瞬时外向钾电流(Ito)、L型钙电流(ICa-L)及其基因表达的影响。方法普通杂种犬30只,分为假手术(S)组、心房起搏对照(C)组、依那普利(EN)组、厄贝沙坦(IB)组及Ang-(1-7)(A)组,每组6只。C组以特制起搏器维持500次/分右房起搏2周,S组安置起搏器但不予起搏刺激。EN组、IB组和A组,右房起搏同时分别给予依那普利、厄贝沙坦、Ang-(1-7)治疗至实验结束。观察心房肌细胞Ito、ICa-L和动作电位时程(APD)的变化,以及ItoKv4.3亚单位和ICa-Lα1C亚单位mRNA在心房组织的表达。结果与S组比较,心房起搏后,各刺激频率下C组和EN组APD复极达90%时程(APD90)显著缩短。IB组和A组,APD90缩短不显著。S组、IB组、A组,随着刺激频率增加APD90缩短,C组、EN组无此特征。除EN组外,不同刺激频率下,各组复极达50%时程(APD50)变化均不显著。与S组比较,C组、IB组Ito最大电流密度显著降低(P<0.05),EN组显著升高(P<0.01);C组、EN组、IB组ICa-L最大电流密度低于S组(P<0.01)。C组、IB组Kv4.3mRNA转录水平低于S组(P<0.01),EN组显著升高(P<0.01)。C组、EN组、IB组、A组ICa-Lα1CmRNA转录水平较S组显著降低(P<0.01)。结论依那普利、厄贝沙坦和Ang-(1-7)对快速心房起搏犬心房肌Ito、ICa-L及APD的影响不同。
Objective To evaluate the effects of enalapril, irbesartan, and Ang-（1-7） on transient outward K ^＋ current （ Ito ）, L-type Ca^2 = current （ICa-L ） and related mRNA expression of atrial myocytes in atrial tachycardia canine model. Methods Thirty mongrel dogs were randomly assigned to sham, paced, enalapril, irbesartan or Ang-（1-7） group respectively. Right atrial pacing at 500 beats per minute was maintained for a period of 14 days in paced group, the sham dogs were instrumented without pacing. The dogs in enalapril, irbesartan, and Ang-（1-7） groups received enalapril, irbesartan or Ang-（1-7） treatment during atrial pacing respectively. At the end of the experiments, Ito, ICa-L and action potential duration （APD） were recorded, and atrial mRNA of I,o Kv4.3 and ICa-L α1C subunits were quantified. Results Compared with sham, after the pacing, APD9o of atrial myocytes from paced group and enalapril group were shortened at various cycle lengths, APD90 wasn＇t shortened in irbesartan group and Ang-（1-7） group. The atrial myocytes from sham group, irbesartan group and Ang-（1-7） group showed APD90 rate adaptation, but the rate adaptation was lost in paced group and enalapril group. APD50 wasn＇t changed significantly, except in enalapril group APD50 was shortened at some cycle lengths. The density of Ito and mRNA of Kv4.3 were reduced in paced group and irbesartan group （P 〈 0.05, vs sham）, but were increased in enalapril group （P 〈0.01, vs sham） . The density of ICa-L was reduced in paced group, enalapril group and irbesartan group （P 〈 0.01, vs sham）. The mRNA of I Ca-Lα1 C was reduced in paced group, enalapril group, irbesartan group and Ang-（1-7） group （P〈0.01 vs sham）. Conclusion These results suggest that enalapril, irbesartan, and Ang-（1-7） have different influences on atrial tachycardia-induced Ito, ICa-L and APD changes in atrium. [ Chinese Journal of Cardiac Pacing and Electrophysiology,2010,24（ 2 ） ：156 -161 ]
出处
《中国心脏起搏与心电生理杂志》
北大核心
2010年第2期156-161,共6页
Chinese Journal of Cardiac Pacing and Electrophysiology
基金
国家自然科学基金资助(项目编号:30770863)
