比索洛尔对心衰大鼠心室肌瞬时外向钾通道蛋白表达的影响

Effect of bisoprolol on protein expression of transient outward potassium channel in ventricle of heart failure rats

目的观察比索洛尔对容量超负荷心衰大鼠左室心肌瞬时外向钾通道(I to)蛋白表达的影响。方法成年雄性SD大鼠(180-200 g)随机分为假手术组(n=16)、心衰组(n=20)和比索洛尔干预组(n=20),采用腹主动脉-下腔静脉穿刺造瘘法制作容量超负荷心衰模型。术后8周,比索洛尔干预组给予比索洛尔(1 mg/kg,1次/d)灌胃,干预4周后,检测血流动力学及血清脑钠肽(BNP)以评价心功能,采用免疫荧光染色和Western blot测定各组大鼠左室心肌I to通道的亚型K v1.4、K v4.2、K v4.3的蛋白表达量。结果心衰组与假手术组大鼠比较,血流动力学状况明显下降,BNP明显升高(P<0.01)。假手术组K v1.4、K v4.2、K v4.3在细胞膜及细胞浆中均表达,以K v4.3表达为主,心衰组K v1.4、K v4.3的蛋白表达量较假手术组明显下降(P<0.01);比索洛尔干预可明显改善心功能及血流动力学状况,增加K v1.4、K v4.3的蛋白表达量(P<0.01或P<0.05)。结论比索洛尔干预可改善慢性心衰大鼠的心功能,增加I to通道的亚型K v1.4、K v4.3的蛋白表达量。

Objective To observe the effect of bisoprolol on protein expression of transient outward potassium channel(I to)in the left ventricle of volume-overload heart failure rats.Methods Adult male SD rats(180-200 g)were randomly divided into sham group(n=16),heart failure(HF)group(n=20)and bisoprolol group(n=20).Heart failure rats were created by abdominal arteriovenous fistula.At 8 week after operation,the rats in bisoprolol group were given bisoprolol(1 mg/kg,once a day).After 4 weeks of intervention,hemodynamics and brain natriuretic peptide(BNP)were detected to evaluate heart function.The protein expression of K v1.4,K v4.2,K v4.3 in left ventricle was evaluated by immunohistochemistry and Western blot.Results Compared with sham group,hemodynamic parameters were decreased and BNP was increased in heart failure group(P<0.01).K v1.4,K v4.2,K v4.3 were expressed in cell membrane and cytoplasm in sham group.The protein expression of K v1.4,K v4.3 was lower in heart failure group than in sham group.BNP level was lower in bisoprolol group than in heart failure group,and hemodynamic parameters and protein expression of K v1.4,K v4.3 were higher in bisoprolol group than in heart failure group(P<0.01 or P<0.05).Conclusion Bisoprolol could improve cardiac function of rats with chronic heart failure by increasing the protein expression of subtypes K v1.4 and K v4.3 of I to channel.