奈必洛尔对L-NAME致高血压大鼠左心室重构和Cx43表达的影响

Effect of nebivolol on left ventricular and Cx43 remodeling in L-NAME-induced hypertensive rats

目的观察奈必洛尔对L-NAME致高血压大鼠左心室重构及心肌连接蛋白43(connexin 43,Cx43)表达的影响。方法将24只Wistar大鼠随机分为4组:空白对照组、模型组、奈必洛尔组和阿替洛尔组。除空白对照组,其余三组给予LNAME(60 mg/kg)制备高血压模型鼠,药物治疗组同时分别给予奈必洛尔(8 mg/kg)和阿替洛尔(80 mg/kg)。给药8周,期间每周测定一次收缩压。实验结束后,3%戊巴比妥钠(30 mg/kg)麻醉大鼠,快速分离心脏,免疫组化和Western blot观察左心室Cx43分布和蛋白表达。结果与空白对照组比较,模型组大鼠在给予L-NAME 1周后血压逐渐升高,到给药第8周时高达(192.36±6.95)mm Hg。奈必洛尔组血压较模型组显著降低,且明显较阿替洛尔组低。模型组左心室重构,Cx43蛋白表达降低。奈必洛尔抑制左心室重构,增加Cx43表达,改善L-NAME致高血压大鼠Cx43排列紊乱,但阿替洛尔仅增加Cx43表达(P<0.05),对左心室重构无显著影响。结论奈必洛尔在显著降压的同时,可改善L-NAME高血压大鼠左心室重构,增加心肌Cx43表达。

Objective To explore the effect of nebivololon on left ventricular remodeling and Cx43 expression in L-NAME-induced hypertensive rats. Methods All Wistar rats were randomly divided into 4 groups：blank control group,model group,nebivolol group and atenolol group. The model rats were induced by L-NAME. The rats were respectively administered with nebivolol and atenolol for 8weeks in nebivolol group and atenolol group. The systolic blood pressure was measured every week during the treatment. At the end of experiment,the structure of left ventricle was observed using HE staining. Immunohistochemistry and Western blot were used to observe the expression of Cx43 in the left ventricle of rats. Results Compared with control group,the blood pressure was significantly increased at 1 week in model group（ P〈0. 05）,and reached（192. 36 ± 6. 95）mm Hg at 8 week. The blood pressure in nebivolol group was significantly lower than in model group and atenolol group（ P〈 0. 05）. In nebivolol group,the L-NAME-induced arrangement of Cx43 and left ventricular remodeling were alleviated and the decreased expression of Cx43 was increased. While atenolol just had an influence on Cx43 expression but not left ventricular remodeling. Conclusion Nebivolol may reduce the blood pressure and increase the expression of Cx43 in L-NAME-induced hypertensive rats,therefore inhibit the remodeling of left ventricular.