摘要
目的观察比索洛尔对容量超负荷心衰大鼠左室心肌细胞瞬时外向钾电流(Ito)的影响。方法成年雄性SD大鼠(180~200g)随机分为正常组、假手术组、心衰组和比索洛尔干预组,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(1mg/kg,1次/日)灌胃,干预4周后,检测血流动力学及脑钠肽(BNP)以评价心功能。急性酶解法分离大鼠左室心肌细胞,采用全细胞膜片钳技术记录Ito电流,并绘制I-V曲线及激活、失活、恢复曲线。结果心衰组与假手术组大鼠比较,心功能明显下降,QTc间期明显延长(198.52±3.90ms vs.163.23±4.15ms,P<0.01),Ito电流密度在-20m V^+90m V明显减小(P<0.05),其失活过程延迟(V1/2:-34.60±0.40m V vs.-38.40±0.46m V;k:5.92±0.35 vs.7.78±0.41,P<0.05),激活曲线及恢复曲线无明显变化。比索洛尔干预可明显改善心功能,缩短QTc(180.32±5.43ms vs.198.52±3.90ms,P<0.01),增加Ito电流密度,改善失活过程(V1/2:-38.62±0.37m V vs.-34.60±0.40m V;k:6.7±0.3 vs.5.92±0.35,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Ito电流密度。
Objective To explore the effect of bisoprolol on transient outward potassium current（Ito） in left ventricular cardiomyocytes of volume-overload heart failure rats. Methods Adult male SD rats（180~200 g） were randomly divided into normal, sham operation, heart failure and bisoprolol treatment group. Volume-overload heart failure rats were created by 8 weeks abdominal arteriovenous fistula, then bisoprolol（1 mg/kg, qd） was administrated for 4 weeks. Hemodynamics and brain natriuretic peptide（BNP） were studied to evaluate heart function. Ito was recorded by whole cell patch clamp technique. Results Compared with the SO group, heart function decreased in HF group. And QTc was prolonged（198.52±3.90 ms vs. 163.23±4.15 ms, P〈0.01）, the current density of Ito was decreased in-20 m V ~ ＋90 m V（P〈0.05）, the inactivation process was delayed in HF group（V1/2：-34.60±0.40 m V vs.-38.40±0.46 m V; k： 5.92±0.35 vs. 7.78±0.41, P〈0.05）. Long term treatment with bisoprolol could improve heart function, shorten the QTc（180.32±5.43 ms vs. 198.52±3.90 ms, P〈0.01）, increase the density of Ito and improve the inactivation process（V1/2：-38.62±0.37 m V vs.-34.60±0.40 m V; k： 6.7±0.3 vs. 5.92±0.35, P〈0.05）. Conclusion Bisoprolol could ameliorate cardiac function and down-regulate Ito in HF rats.
作者
王建丽
马爱群
汪克纯
王贺
王亭忠
WANG Jian-li;MA Ai-qun;WANG Ke-chun;WANG He;WANG Ting-zhong(Department of Cardiovascular Medicine, Sixth People＇s Hospital of Chengdu, Chengdu 610051, China.)
出处
《中国分子心脏病学杂志》
CAS
2018年第1期2372-2375,共4页
Molecular Cardiology of China
基金
国家自然科学基金重点项目(30830051)
关键词
比索洛尔
心力衰竭
瞬时外向钾电流
大鼠
Bisoprolol
Heart Failure
Transient Outward Potassium Current
Rat
