替米沙坦对“两肾一夹”大鼠心房肌瞬时外向钾通道和L型钙通道表达的影响

Effect of telmisartan on transient outward potassium current and L-type calcium current of atrial myocardium in ‘two kidney one clip’ rats

目的:本实验研究替米沙坦对"两肾一夹"(Two kidney one clip,2K1C)SD大鼠心房肌细胞瞬时外向钾通道Ito和L型钙通道ICa-Lα亚基编码基因(Kcnd2和Cacna1c)的mRNA和蛋白(Kv4.2和Cav1.2)变化的影响。方法:雄性SD大鼠39只,分成4组:对照组、2K1C+替米沙坦低剂量组[5 mg/(kg.d)]、2K1C+替米沙坦高剂量组[10 mg/(kg.d)]和2K1C组。用药4周后采用反转录聚合酶链反应及免疫印记反应(Western blot)方法分别测定Kcnd2、Cacna1c的mRNA及蛋白水平并对结果进行半定量分析。结果:2K1C组Kcnd2的mRNA及蛋白水平低于对照组(0.23±0.02 vs.1.0±0.12,0.34±0.11 vs.0.78±0.13,P<0.01),Cacna1c高于对照组(1.54±0.17 vs.1.0±0.13,1.58±0.09 vs.0.92±0.05,P<0.01);替米沙坦5、10 mg组Kcnd2的mRNA及蛋白水平均高于2K1C组(0.32±0.01,0.53±0.11 vs.0.23±0.02;0.54±0.07,0.72±0.08 vs.0.34±0.11,P<0.01),Cacna1c低于2K1C组(1.21±0.18,1.02±0.14 vs.1.54±0.17;1.21±0.06,0.98±0.07 vs.1.58±0.09,P<0.01)。结论:替米沙坦通过调节Kcnd2和Cac-na1c的mRNA和蛋白水平来发挥其抗心律失常作用。

Objective：To investigate the effects of telmisartan on transient outward potassium currents（Ito） and L-type calcium currents（ICa-L） of atrial myocardium in two kidney one clip（2K1C） rats by measuring the alteration of mRNA and protein（Kv4.2 and Cav1.2） levels in encoding genes（Kcnd2 and Cacna1c）.Methods： Totally 39 male Sprague-Dawley rats were divided into control group,2K1C and Telmisartan 5 mg/（kg·d） group,2K1C and telmisartan[10 mg/（kg·d）] group and 2K1C group.After four weeks of treatment,mRNA and protein levels of Kcnd2 and Cacna1c were assessed by reverse transcriptase polymerase chain reaction and western blot.The data were analyzed by relative quantification.Results：The expression levels of mRNA and protein of Kcnd2 were decreased{（0.23±0.02） vs.（1.0±0.12）;（0.34±0.11） vs.（0.78±0.13）,P0.01},but those of Cacna1c were increased{（1.54±0.17）vs.（1.0±0.13）;（1.58±0.09） vs.（0.92±0.05）,P0.01} in 2K1C group compared with those in control group.The expression levels of mRNA and protein of Kcnd2 were increased{（0.32±0.01）,（0.53±0.11） vs.（0.23±0.02）;（0.54±0.07）,（0.72±0.08） vs.（0.34±0.11）,P0.01},but those of Cacna1c were decreased{（1.21±0.18）,（1.02±0.14） vs.（1.54±0.17）;（1.21±0.06）,（0.98±0.07） vs.（1.58±0.09）,P0.01} in 2K1C and Telmisartan 5 mg/（kg·d） group as well as 2K1C and telmisartan 10 mg/（kg·d） group compared with those in 2K1C group.Conclusion：Telmisartan exerts its antiarrhythmic effects by regulating mRNA and protein levels of Kcnd2 and Cacna1c.