目的 观察三氧化二砷(As2O3)对豚鼠心脏QT间期的影响,并初步探讨其对L型通道蛋白mRNA表达的影响。方法 将豚鼠随机分为4组,分别为正常对照组、As2O3大、中、小剂量组。实验组豚鼠静脉给予不同剂量的As2O3(大剂量组1.6mg/kg、中剂量组0.8mg/kg和小剂量组0.4mg/kg),分别测量不同时间点的心电图,观察QTc(校正的QT间期)的变化。提取心肌组织总RNA,用RT-PCR方法观察As2O3对豚鼠心肌L型Ca^2+通道蛋白mRNA表达的影响。结果 在2h的观察时间内,0.8mg/kg和1.6mg/kg As2O3分别使QTc从对照组的(324±20)ms延长到(368±29)ms(P〈0.01)和(388±31)ms(P〈0.01)。RT-PCR结果显示1.6mg/kg As2O3可以使豚鼠心肌L型钙通道mRNA表达增强(与对照组相比,P〈0.01)。结论 As2O3可引起豚鼠心脏叫间期延长,其机制可能与增强L型钙通道蛋白mRNA表达有关。
Objective To observe the effect of arsenic trioxide (As2O3 ) on QT interval of guinea pig electrocardiogram and investigate the effect of As2O3 on the L-type calcium channel mRNA expression in the cardiomyocytes of guinea pig. Methods The guinea pigs were divided into 4 groups randomly: control group, high dose group, middle dose group and low dose group. The experiment guinea pigs were given 1,6mg/kg (high dose group ), 0.8mg/kg ( middle dose group) and 0.4mg/kg ( low dose group) of As2O3, respectively. The electrocardiograms of those guinea pigs were measured and the corrected QT intervals (QTc) were cacaulated and competed. Total RNAs were extracted from the cardiomyocytes of the guinea pigs. RT-PCR was used to study the effects of As2O3 on L-type calcium channel mRNA expression in cardiomyocytes of guinea pigs.Results As2O3 at concentrations of 0.8mg/kg and 1.6mg/kg prolonged the QTc from (324±20) ms to (368±29) ms (P 〈 0.01 ), and (388±31 ) ms ( P 〈 0.01 ), respectively. The RT-PCR studies showed that 1.6mg/kg of As2O3 enhanced the L-type calcium channel mRNA expression (compared with control groups, P 〈 0.01). Conclusion As2O3 could prolong the QT interval of guinea pig cardiomyocyte. The possible mechanism was associated with the upregulation of the L-type calcium channel mRNA expression due to the exposure to As2O3.