脑钠肽对大鼠心脏重构和心电生理效应的作用

Effect of B-type natriuretic peptide on cardiac remodeling and electrophysiology in rats

目的观察大鼠长时间使用重组人脑钠肽(recombinant human B-type natriuretic peptide,rhBNP)后产生的心电生理效应和心脏重构效应,并与心肌梗死后大鼠进行对比。方法雄性健康Wistar大鼠60只,分为3组:正常对照组、脑钠肽(B-type natriuretic peptide,BNP)处理组和心肌梗死组。以结扎左前降支的方法制作大鼠心肌梗死模型,正常对照组和BNP处理组进行假手术。BNP处理组予以国产冻干rhBNP(新活素)持续静脉微泵推注,连续输注7 d。用超声心动图评估并对比3组大鼠心脏左心室质量,左心室缩短分数,左心室舒张末期直径。用24小时动态心电图监测记录并对比3组大鼠心率变异性(heart rate variability,HRV),PR间期,QRS间期,QTC间期等参数以及心律失常情况。结果长时间rhBNP灌注可升高BNP处理组大鼠的心脏质量/体质量比,心肌梗死组也发生了类似的变化,与正常对照组比较差异有统计学意义(P<0.05)。BNP处理组和心肌梗死组QTC间期均拉长,与正常对照组比较差异有统计学意义(P<0.05);SDNN都有明显降低,与正常对照组比较差异有统计学意义(P<0.05)。BNP处理组频率域分析显示低频带有振荡增高,与正常对照组比较差异有统计学意义[(0.08±0.02)ms2vs.(0.05±0.01)ms2,P<0.05];低频/高频比率增高,与正常对照组比较差异有统计学意义(2.7±0.4 vs.1.3±0.2,P<0.05)。对比正常对照组,在BNP处理组和心肌梗死组大鼠观察到更多如频发室性期前收缩和室性心动过速等室性心律失常。结论长时间使用rhBNP可能引发大鼠心脏重构效应和交感神经张力升高,进而诱发室性心律失常。

Objectives To investigate the cardiac effects of chronic recombinant human B-type natriuretic peptide （rhBNP） in healthy rats and compared the results with those in rats with myocardial infarction.Methods Sixty healthy adult male Wistar rats were divided into three groups：control group,post-myocardial infarction （PMI） group and B-type natriuretic peptide （BNP）-sham group.The chest of rats in PMI group was opened and a ligature was placed around the left anterior descending coronary artery.Rats in control and BNP-sham groups were sham-operated without the coronary artery ligation.For rats in BNP-sham group,rhBNP was administered at a rate of 0.06 μg/（kg·min） for 7 days,using a micro-osmotic pump.Left ventricular mass,left ventricular shortening fraction and left ventricular end-diastolic diameter of all the rats were measured and compared by echocardiography.Heart rate variability （HRV）,the PR,QRS and QTC intervals,and arrhythmias were analyzed using Holter.Results Chronic rhBNP treatment obviously increased the heart weight/body weight ratio of BNP-sham and so was the PMI rats （P〈0.05）.QTC interval significantly increased in both BNP-sham and PMI rats （P〈0.05）.SDNN comparably decreased in BNP-sham and PMI rats （P〈0.05）.Frequency-domain analysis showed that low-frequency oscillations [（0.08 ±0.02） ms2 vs.（0.05 ±0.01） ms2,P〈0.05],the lowfrequency/high-frequency ratio （2.7±0.4 vs.1.3±0.2,P〈0.05） significantly increased in BNP-sham rats （P〈0.05）.In contrast,more ventricular arrhythmias （VAs） were observed in BNP-sham and PMI rats.Conclusions Chronic rhBNP treatment can trigger VAs in rats,probably by inducing sympathetic overdrive and cardiac remodeling.