三氧化二砷诱导豚鼠心脏QT间期延长及其分子机制研究  

Effects of arsenic trioxide on QT interval and potassium channel protein mRNA expression in guinea pig hearts

作　　者：王晓慧[1] 孙宏丽[1] 霍蓉[1] 王宁[1] 董德利[1] 孙建平[1] 吕延杰[1] 杨宝峰[1] 

机构地区：[1]哈尔滨医科大学药理教研室,黑龙江省生物医药重点实验室,150081

出　　处：《中国地方病学杂志》2007年第4期394-396,共3页Chinese Jouranl of Endemiology

基　　金：国家自然科学基金重点项目（30430780）

摘　　要：目的 观察三氧化二砷（As2O3）对豚鼠心脏QT间期的影响，并探讨其对延迟整流钾通道蛋白mRNA表达的影响。方法 按静脉给予的As2O3剂量，将豚鼠随机分为4组：0（对照组）、0．4、0．8、1．6mg／kg组。测量不同时间点的心电图，观察校正QT间期（QTc）的变化。用反转录聚合酶链式反应（RT—PCR）方法观察As2O3对心肌延迟整流钾通道蛋白mRNA表达的影响。结果 在120min时，As2O3 0．8、1．6mg／kg组QTc分别为（368±29）、（388±31）ms，与对照组[（324±20）ms]比较，明显延长（t值分别为9．26、16．37，P〈0．01）。RT-PCR结果显示，与对照组比较，As2O3,1．6mg／kg可以使豚鼠心肌缓慢型延迟整流钾通道蛋白（KvLQT1）mRNA表达降低（t=12．83，P〈0．01），而对快速型延迟整流钾通道蛋白（ERG）mRNA表达则无明显影响。结论 As2O3可引起豚鼠心脏QT间期延长，其机制可能与抑制KvLQT1 mRNA表达有关。Objective To observe the effects of arsenic trioxide（As2O3） on QT interval of the electrocardiogram of guinea pig and to further investigate the effect of As2O3 on the potassium channel protein mRNA expression in the cardiomyocyte of guinea pig. Methods The guinea pigs were divided into 4 groups randomly： 0 （control group）, 0.4,0.8,1.6 mg/kg As2O3. Then, corrected QT interval（QTc ） was measured at different time. Total RNA was extracted from the cardiomyocytes of guinea pigs. The method of reverse transcription polymerase chain reaction was used to study the effects of As2O3 on potassium channel protein mRNA expression in cardiomyocytes of guinea pigs. Results As2O3 at concentrations of 0.8,1.6 mg/kg prolonged QTc from （324 ± 20）ms to （368 ± 29）ms （F = 9.26, P 〈 0.01） and （388 ± 31）ms respectively （F= 16.37,P 〈 0.01）. The RT-PCR studies showed that 1.6 mg/kg As203 inhibited the potassium channel protein mRNA expression （compared with control groups, F = 12.83,P 〈 0.01）. Conclusions As2O3 could prolong the QT interval of guinea pig cardiomyoeyte. The possible mechanism was associated with the inhibition of the potassium channel KvLQT1 mRNA expression from the exposure to As2O3.

关 键 词：三氧化二砷 QT间期 延迟整流钾通道 

分 类 号：R686[医药卫生—骨科学]