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目的:观察不同剂量的三氧化二砷(arsenic trioxide,As2O3)对心肌细胞膜上延迟整流钾电流蛋白表达的影响。方法:将豚鼠随机分为4组:正常对照组、As2O3小剂量组(0.4 mg/kg)、中剂量组(0.8 mg/kg)、大剂量组(1.6 mg/kg),给药后不同时间间隔记录心电图,测量QT间期和RR间期,计算QTc的值的变化,同时应用荧光免疫组化技术检测心肌延迟整流钾通道IKr、IKs通道蛋白的表达量。结果:1在不同剂量的As2O3作用下,0.8 mg/kg和1.6 mg/kg As2O3组的豚鼠QTc明显延长,并且这种延长作用与给药剂量和时间密切相关。在2 h的观察时间内,0.8 mg/kg和1.6 mg/kg As2O3分别使QTc从对照组的324±7 ms延长到368±11 ms(P<0.01)和388±11 ms(P<0.01)。2大剂量组豚鼠心肌缓慢型延迟整流钾通道Kv LQT1和GPERG蛋白表达与对照组相比显著降低(P<0.01)。结论:As2O3对豚鼠心肌QT间期有明显延长效果,其机制可能与降低Kv LQT1和GPERG蛋白的表达,影响了钾通道的功能有关。
OBJECTIVE: To observe the effect of arsenic trioxide (As2O3) on the expression of delayed rectifier K + current in myocardial cells. Methods: Guinea pigs were randomly divided into 4 groups: normal control group, low dose of As2O3 (0.4 mg / kg), middle dose of 0.8 mg / kg, high dose of 1.6 mg / kg, The electrocardiogram (ECG) was recorded at intervals. QT interval and RR interval were measured to calculate the change of QTc value. At the same time, the expression of IKr and IKs channel protein in delayed rectifier potassium channel was detected by fluorescence immunohistochemistry. Results: 1 Under the different doses of As2O3, QTc of guinea pigs in 0.8 mg / kg and 1.6 mg / kg As2O3 groups were significantly prolonged, and this prolongation was closely related to the dosage and time. At 2 h, QTc was prolonged from 324 ± 7 ms to 368 ± 11 ms (P <0.01) and 388 ± 11 ms (P <0.01), respectively, at 0.8 mg / kg and 1.6 mg / . 2 The expression of Kv LQT1 and GPERG in chronic delayed-rectifier potassium channel of guinea pigs in high-dose group was significantly lower than that in control group (P <0.01). CONCLUSION: As2O3 can significantly prolong the QT interval of guinea pig myocardium, and its mechanism may be related to the decrease of Kv LQT1 and GPERG protein expression and the influence of potassium channel function.