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甲状腺素心肌病大鼠血流动力学和心肌钠、钙电流的变化

王静, 张伟东, 林木森, 翟清波, 于锋^*

中国药科大学临床药学研究室，南京210009

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0.5 mg/kg 腹腔注射L-thy，连续注射10 d，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(left ventricular systolic pressure, LVSP)、左心室发展压(left ventriculardeveloped 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-30 mV 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。

关键词： L-甲状腺素; 心肌病; 血流动力学; I Na; I C a - L; 全细胞膜片钳

分类号：R36

[Alterations of cardiac hemodynamics, sodium current and L-type calcium current in rats with L-thyroxine-induced cardiomyopathy.] [Ariticle in Chinese]

Wang Jing, ZHANG Wei-Dong, LIN Mu-Sen, ZHAI Qing-Bo, YU Feng^*

Department of Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, China

Abstract

The aim of the present study is to investigate the alterations of cardiac hemodynamics, sodium current (INa) and L-typecalcium current (ICa-L) in the cardiomyopathic model of rats. The model of cardiomyopathy was established by intraperitoneal injectionof L-thyroxine (0.5 mg/kg) for 10 d. The hemodynamics was measured with biological experimental system, and then INa and ICa-Lwererecorded by using whole cell patch clamp technique. The results showed that left ventricular systolic pressure (LVSP), left ventriculardeveloped pressure (LVDP), ±dp/dtmax in cardiomyopathic group were significantly lower than those in the control group, while leftventricular end-diastolic pressure (LVEDP) in cardiomyopathic group was higher than that in the control group. Intraperitonealinjection of L-thyroxine significantly increased the current density of INa [(-26.2±3.2) pA/pF vs (-21.1±6.3) pA/pF, P<0.01], shiftedsteady-state activation and inactivation curves negatively, and markedly prolonged the time constant of recovery from inactivation. Onthe 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,P<0.01)], shifted steady-state activation and inactivation curves negatively, and obviously shortened the time constant of recoveryfrom inactivation. In conclusion, the cardiac performance of cardiomyopathic rats is similar to that of rats with heart failure, in whichthe current density of INa and especially the ICa-L are enhanced, suggesting that calcium channel blockade and a decrease in Na+ permeabilityof membrane may play an important role in the treatment of cardiomyopathy.

Key words: L-thyroxine; cardiomyopathy; hemodynamics; INa; ICa-L; patch clamp

收稿日期：2010-04-29　　录用日期：2010-07-13

通讯作者：于锋　　E-mail: yufengcpu@163.com

引用本文：

王静, 张伟东, 林木森, 翟清波, 于锋. 甲状腺素心肌病大鼠血流动力学和心肌钠、钙电流的变化[J]. 生理学报 2010; 62 (4): 325-332.

Wang Jing, ZHANG Wei-Dong, LIN Mu-Sen, ZHAI Qing-Bo, YU Feng. [Alterations of cardiac hemodynamics, sodium current and L-type calcium current in rats with L-thyroxine-induced cardiomyopathy.] [Ariticle in Chinese] . Acta Physiol Sin 2010; 62 (4): 325-332 (in Chinese with English abstract).