长期给予左甲状腺素对大鼠心室肌细胞L-型钙通道的影响

Effect of long-term administration of levo-thyroxine on ICa,L density in the remodeled rat hearts

目的:观察长期给予左甲状腺素对大鼠血流动力学及心肌细胞膜L-型钙通道的影响。方法:大鼠口服左甲状腺素(levo-thyroxine,L-thy)40d:第1～10天给予L-thy2mg/kg;第11～40天剂量降至1mg/kg。运用生物实验系统观察大鼠血流动力学的改变,测定血清中T4水平以及心肌中谷胱苷肽GSH含量和乳酸脱氢酶LDH活力,全细胞膜片钳技术观察心室肌细胞L-型钙通道的变化。结果:与正常组相比,模型组T4升高33.5%(P<0.05),LVEDP显著升高,+dp/dtmax明显下降,T值显著延长。提示L-thy给药40d后,大鼠心脏收缩和舒张功能均降低。心肌GSH下降23.6%,LDH活力增加28%;全细胞膜片钳实验表明,L-thy给予40d后,大鼠心室肌细胞钙电流峰值降低47%(P<0.01),半激活电压从(-18.9±0.6)mV右移到(-14.8±0.7)mV(P<0.01),半失活电压从(-25.1±0.9)mV右移到(-21.7±0.9)mV(P<0.01),失活恢复常数从(102.2±2.1)ms延长到(136.9±2.5)ms(P<0.01)。结论:左甲状腺素给药40d可致大鼠心收缩,舒张功能降低,心肌细胞钙离子通功能下降。

Aim：To observe L-type calcium channel in ventricular myocytes from the rat heart failure induced by L- thyroxine. Methods： Animal model was obtained by intragastric administration of L-thyroxine 2 mg/kg for 10 days, which was then switched to 1 mg/kg in the next 30 days. Cardiac function was assessed by the measurement of the level of thyroid hormone level （T4） in serum as well as GSH and LDH in cardiac muscle. L-type calcium channel was recorded by the whole-cell patch clamp technology between the normal and L-thyroxine groups. Results： In L-thyro- xine group, the level of T4 was increased by 33.5 % （P 〈 0.05） ; LVEDP was significantly elevated; ＋dp/d t was profoundly decreased by 12% ; and T was prolonged. The levels of T4 and LDH were increased sharply in L-thy group, while GSH was decreased by 23.6% （ P 〈 0.05）. Ica, L from L-thyroxine group were attenuated by 47% ,while steadystate activation and inactivation shifted right, time constant of recovery from inactivation was extended markedly. Conclusion：40-day administration of L-thyroxine could change the ventricular systolic and diastolic functions and the animal model is associated with the descrease in L-thyroxine Ca^2＋ channel.