厄贝沙坦对心力衰竭大鼠心肌电生理失稳态和心室肌细胞I_(Ca-L)电流的影响  

Effect of Irbesartan on Electrical Instability and L-type Calcium Channel Current in Failing Hearts of Rats

作　　者：褚春[1] 杨军[2] 王苏燕[2] 邓彪[2] 丁赛良[2] 王光辉[2] 张勇[2] 伍卫[3] 

机构地区：[1]南华大学第二附属医院药剂科,湖南衡阳421001 [2]南华大学第一附属医院心内科 [3]中山大学附属第二医院心内科

出　　处：《中南医学科学杂志》2012年第1期42-46,共5页Medical Science Journal of Central South China

基　　金：湖南省卫生厅课题(项目编号B2010-051)资助

摘　　要：目的探讨厄贝沙坦对心力衰竭大鼠心室电生理失稳态和L-型钙通道电流的影响。方法采用腹主动脉缩窄法建立大鼠心力衰竭模型,随机分两组,即心力衰竭治疗组与心力衰竭对照组,分别用厄贝沙坦(20mg/kg)和安慰剂治疗,另设假手术对照组。在术后32周用测定3组大鼠电生理指标以及心功能,以急性酶解法获得单个大鼠心室肌细胞并以标准全细胞膜片钳技术记录钙通道电流。结果与假手术对照组相比,心力衰竭治疗组与心力衰竭对照组大鼠的左室舒张末压、心率和动脉血压均明显增加,而心力衰竭对照组大鼠校正QT间期和VERP明显延长,QT离散度增加,心力衰竭治疗组与心力衰竭对照组相比左心室VERP明显缩短,且心力衰竭对照组的细胞膜电容大于假手术对照组(P<0.05),亦明显大于心力衰竭治疗组(P<0.05),心力衰竭对照组L-型钙通道电流峰值(-926.28±334.26 pF)及电流密度(-12.61±4.55 pA/pF)稍少于假手术对照组(-921.87±468.56 pF和-13.83±7.04 pA/pF),但差异无显著性(P>0.05),但心力衰竭治疗组L-型钙通道电流峰值(-423.47±100.80 pF)及电流密度(-7.02±1.66 pA/pF)明显低于心力衰竭对照组和假手术对照组(P<0.05)。3组L-型钙通道电流的激活、失活和复活动力学特征差异均无显著性(P>0.05)。结论厄贝沙坦能明显改善心力衰竭大鼠电生理失稳态变化,并可能与其下调L-型钙通道电流有关。Objective To determine the effects of Irbesartan on cardiac electrical instability and L-type calcium channel current（ICa-L）in isolated ventricular myocytes of congestive heart failure rats.Methods A heart failure model of experimental pressure overload induced by surgical abdominal aortic stenosis in adult SD rats was used in this study.16 weeks later,the rats with heart failure were confirmed by measuring the hemodynamic parameters and divided randomly into the groups treating with Iirbesartan（CHF-T group,20 mg/kg） and placebo（CHF-C group） for 16 weeks.Sham-operated group served as negative controls（PS group）.The right femoral artery of the rat was isolated and was cannulated with a catheter for recording blood pressure and left ventricular end-diastolic pressure.Then cardiac electrophysiological parameters including ventricular effective refractory period（VERP） in left ventricle were measured.The electrodes were inserted into four limbs of rat for surface electrocardiogram.Single ventricular myocytes of rats were isolated by enzymatic dissociation.The whole-cell patch-clamp recording technique was used to record ICa-L.Results Compared with PS group,heart rate,QT-interval and VERP of rat in CHF-C group increased.Heart rate,the QT-interval and VERP of rat in CHF-T group decreased compared with CHF-C group.The ICa-L in CHF-T group was significantly larger than that in CHF-C group（P0.05）.Compared with in PS group,the current density of of ICa-L was unchanged（P0.05） in myocytes of left venticle from CHF-C group.Compared with that from CHF-C group and PS group,the current density of ICa-L in myocytes of left ventricle from CHF-T group downregulated significantly.The activation,inactivation and recovery curves were not altered in 3 groups（P0.05）.Conclusion Administration of Irbesartan is effective in preventing from cardiac electrical instability in rats with heart failure and that is maybe related to decreasing ICa-L of ventricular myocytes of heat failure rats.

关 键 词：心力衰竭 厄贝沙坦 电生理 L-型钙通道 

分 类 号：R972[医药卫生—药品]