囊性纤维化跨膜转导调节因子敲除对小鼠心脏结构和功能的影响

Effect of Cystic Fibrosis Transmembrane Conductance Regulator Knockout on Cardiac Structure and Function in Mice

目的探讨囊性纤维化跨膜转导调节因子(cystic fibrosis transmembrane conductance regulator,CFTR)对心脏结构和功能的影响。方法8~10周龄雄性Cftr野生型(Cftr+/+)小鼠为Cftr+/+组(n=20),8~10周龄雄性Cftr基因敲除型(Cftr^(-/-))小鼠为Cftr^(-/-)组(n=20)。两组小鼠植入Transmitter,动态监测心率变化,使用Vevo 2100超声仪行超声心动检查,评估小鼠心脏结构和功能状态。结果Cftr^(-/-)组小鼠24小时心率(heart rate,HR)、白天HR、夜间HR均明显高于Cftr+/+组[(651±38.1)次/min vs(593±35.7)次/min,(632±40.3)次/min vs(582±46.5)次/min,(662±39.0)次/min vs(603±40.2)次/min,P<0.05];Cftr+/+组小鼠和Cftr^(-/-)组小鼠HR的昼夜节律均呈双峰模式,但Cftr^(-/-)组小鼠HR峰值时间较Cftr+/+组小鼠晚2小时。Cftr基因敲除引起左心室壁厚度和左心室腔大小的改变。Cftr^(-/-)组小鼠的射血分数(ejection fraction,EF)和缩短分数(shortening fraction,FS)较Cftr+/+组小鼠下降[(71±5.1)%vs(78±5.3)%,(40±4.2)%vs(46±5.1)%,P<0.05]。与Cftr+/+组小鼠相比,Cftr^(-/-)组小鼠的左心室质量指数(left ventricular mass index,LVMI)、心脏重量与体重比值(HW/BW)明显增加[(116±10.2)g/10m2 vs(105±6.1)g/10m2,52±5.3 vs 42±3.1,P<0.05]。结论CFTR氯离子通道影响小鼠心率和心脏结构功能。

Objective To investigate the effects of cystic fibrosis transmembrane conductance regulator(CFTR)on cardiac structure and function.Methods Male Cftr wild-type(Cftr^(+/+))mice aged 8-10 weeks were Cftr^(+/+)groups(n=20),and male Cftr knockout(Cftr^(-/-))mice aged 8-10 weeks were Cftr^(-/-)groups(n=20).All of them were implanted with transmitter.Heart rate(HR)was monitored by transmitter.Echocardiography was performed with Vevo 2100 ultrasonic instrument.Cardiac function was evaluated by echocardiography.Results The 24-hour,daytime and nighttime HR of Cftr^(-/-)group were significantly higher than those of Cftr^(+/+)group[(651±38.1)beat/min vs(593±35.7)beat/min,(632±40.3)beat/min vs(582±46.5)beat/min,(662±39.0)beat/min vs(603±40.2)beat/min,P<0.05].The circadian rhythm of HR in Cftr^(+/+)group mice and Cftr^(-/-)group mice showed bimodal pattern,but the peak HR time of Cftr^(-/-)group mice was 2 hours later than that of Cftr^(+/+)group mice.Cftr gene knockout caused changes in wall thickness and chamber size of left ventricle.Compared with Cftr^(+/+)group mice,Cftr^(-/-)group mice had decreased ejection fraction(EF)and shortening fraction(FS)[(71±5.1)%vs(78±5.3)%,(40±4.2)%vs(46±5.1)%,P<0.05].Compared with Cftr^(+/+)group mice,left ventricular mass index(LVMI)and heart weight/body weight ratio(HW/BW)of Cftr^(-/-)group mice were significantly increased[(116±10.2)g/10m2 vs(105±6.1)g/10m2,52±5.3 vs 42±3.1,P<0.05].Conclusion CFTR chloride channel affected heart rate,cardiac structure and function.