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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。
This study was designed to investigate the hemodynamics and the currents of INa and ICa-L in rat cardiomyopathy induced by L-thyroxine (L-thy) The change. The experimental rats were randomly divided into two groups: cardiomyopathy group and control group. The cardiomyopathy group was injected intraperitoneally with 0.5mg / kg L-thym for 10 days. The hemodynamic changes were determined after successful modeling. Cardiomyocytes were isolated by acute enzymatic method. Whole cell patch clamp technique was used to record the changes of INa and ICa- L. The results showed that: (1) Compared with the control group, left ventricular systolic pressure (LVSP), left ventricular developed pressure (LVDP) and left ventricular diastolic pressure (-dp / dtmax) and left ventricular end-systolic pressure (-dp / dtmax) decreased significantly (P <0.01) (P <0.01). (2) Compared with the control group, the INa current density of cardiomyocytes in the cardiomyopathy group was (-21.1 ± 6.3) at depolarization potential of -30mV pA / pF increased to (-26.2 ± 3.2) pA / pF (n = 12, P <0.01). The activation curve of INa shifted to the left and the inactivation curve shifted to the left. Compared with the control group, the ICa-L current density of cardiomyocytes increased from (-5.4 ± 0.6) pA / pF to (-7.9 ± 0.8) pA / pF (n = 12, P <0.01). The activation curve of ICa-L shifted to the left, the inactivation curve shifted to the left and the deactivation curve moved to the left. The above results show that the thyroid hormone cardiomyopathy model heart function similar to heart failure, its INa and ICa-L function was significantly increased, especially ICa-L, suggesting that in INa and ICa-L dysfunction cardiomyopathy treatment if used Calcium channel antagonists should be better with drugs that reduce myocardial permeability to Na +.