甲状腺素心肌病大鼠血流动力学和心肌钠、钙电流的变化  

Alterations of cardiac hemodynamics,sodium current and L-type calcium current in rats with L-thyroxine-induced cardiomyopathy

作　　者：王静[1] 张伟东[1] 林木森[1] 翟清波[1] 于锋[1] 

机构地区：[1]中国药科大学临床药学研究室,南京210009

出　　处：《生理学报》2010年第4期325-332,共8页Acta Physiologica Sinica

基　　金：supported by the National Natural Science Foundation of China(No.30572193);the Specialized Research Fund for the Doctoral Program of Higher Education of China(No.20050316009)

摘　　要：本文旨在研究L-甲状腺素(L-thyroxine,L-thy)所致的大鼠心肌病模型上血流动力学及心室肌细胞钠电流(INa)、L-钙通道电流(ICa-L)的变化。实验大鼠随机分成两组:心肌病组和对照组。心肌病组以0.5mg/kg腹腔注射L-thy,连续注射10d,建模成功后测定血流动力学变化,然后急性酶解法分离心肌细胞,应用全细胞膜片钳技术记录心肌细胞INa和ICa-L。结果显示:(1)与对照组相比,心肌病组大鼠左心室收缩压(leftventricular systolic pressure,LVSP)、左心室发展压(left ventricular developed pressure,LVDP)和左心室舒张期室内压最大下降速率(-dp/dtmax)均显著降低(P<0.01),左心室收缩期室内压最大上升速率(+dp/dtmax)也表现为降低(P<0.05),左心室舒张末期压(left ventricular end-diastolic pressure,LVEDP)显著升高(P<0.01);(2)与对照组相比,在去极化电位为-30mV时,心肌病组大鼠心肌细胞INa电流密度由(-21.1±6.3)pA/pF增大至(-26.2±3.2)pA/pF(n=12,P<0.01),INa的激活曲线左移,失活曲线左移,去失活曲线右移;(3)与对照组相比,在去极化电位为-10mV时,心肌病组大鼠心肌细胞ICa-L电流密度由(-5.4±0.6)pA/pF增至(-7.9±0.8)pA/pF(n=12,P<0.01),ICa-L的激活曲线左移,失活曲线左移,去失活曲线左移。以上结果表明,甲状腺素心肌病模型心功能与心力衰竭相似,其INa和ICa-L功能明显增强,尤其是ICa-L,提示在INa和ICa-L功能异常增强的心肌病治疗中若使用的钙通道拮抗剂带有降低心肌对Na+通透性的药物效果应更佳。The aim of the present study is to investigate the alterations of cardiac hemodynamics,sodium current（INa） and L-type calcium current（ICa-L） in the cardiomyopathic model of rats.The model of cardiomyopathy was established by intraperitoneal injection of L-thyroxine（0.5 mg/kg） for 10 d.The hemodynamics was measured with biological experimental system,and then INa and ICa-L were recorded by using whole cell patch clamp technique.The results showed that left ventricular systolic pressure（LVSP）,left ventricular developed pressure（LVDP）,±dp/dtmax in cardiomyopathic group were significantly lower than those in the control group,while left ventricular end-diastolic pressure（LVEDP） in cardiomyopathic group was higher than that in the control group.Intraperitoneal injection of L-thyroxine significantly increased the current density of INa [（-26.2±3.2） pA/pF vs（-21.1±6.3） pA/pF,P0.01],shifted steady-state activation and inactivation curves negatively,and markedly prolonged the time constant of recovery from inactivation.On the other hand,the injection of L-thyroxine significantly increased the current density of ICa-L [（-7.9±0.8） pA/pF vs（-5.4±0.6） pA/pF,P0.01）],shifted steady-state activation and inactivation curves negatively,and obviously shortened the time constant of recovery from inactivation.In conclusion,the cardiac performance of cardiomyopathic rats is similar to that of rats with heart failure,in which the current density of INa and especially the ICa-L are enhanced,suggesting that calcium channel blockade and a decrease in Na＋ permeability of membrane may play an important role in the treatment of cardiomyopathy.

关 键 词：L-甲状腺素 心肌病 血流动力学 INa ICA-L 全细胞膜片钳 

分 类 号：R542.2[医药卫生—心血管疾病]