三氧化二砷对心肌细胞膜延迟整流钾通道蛋白表达的影响研究  

Effects of Arsenic Trioxide on Potassium Channel Protein Expression in the Hearts of Guinea Pig

作　　者：王晓慧[1] 崔忠涛[2] 袁瑶薇[1] 王香琛 刘宏[1] 

机构地区：[1]黑龙江中医药大学基础医学院,黑龙江哈尔滨150040 [2]哈尔滨医科大学附属第四医院耳鼻咽喉头颈外科,黑龙江哈尔滨150001

出　　处：《现代生物医学进展》2016年第24期4615-4617,4627,共4页Progress in Modern Biomedicine

基　　金：国家自然科学基金青年基金项目(81403288);黑龙江省青年科学基金项目(QC2015102)

摘　　要：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 effects of different doses of arsenic trioxide （trioxide arsenic, AS203） on the expression of delayed rectifier potassium current in cardiac muscle cells. Methods： Guinea pigs were divided into 4 groups randomly： control group, low dose group （0.4 mg/kg）, middle dose group （0.8 mg/kg） and high dose group （1.6 mg/kg）. Electrocardiogram was recorded at different time intervals after administration, QT interval and RR interval were measured to calculate the value of QTc. At the same time, the expressionS of lKr and IKs channel protein in delayed rectifier potassium channel were detected by fluorescence immunohistochemistry technique. Results：① In different doses of As2O3, 0.8 mg/kg and 1.6 As2O3 mg/kg groups were significantly longer in the QTc group, and the effect was closely related to the dosage and time. As2O3 at the doses of 0.8 mg/kg and 1.6 mg/kg, QTc was gradually prolonged in the 2-hour period observation from 324± 7 ms of control to 368± 11 ms （P〈0.01） and 388± 11 ms （P〈0.01）, respectively.②Compared with the control group, the expression of KvLQT1 and GPERG in the myocardium of the large dose group was significantly lower than that of the control group （P〈0.01）. Conclusions： AS2O3 had significant effect on the QT interval of guinea pig myocardium, and its mechanism might be related to the decrease of fKvLQT1 and GPERG protein expression, thus affecting the fimction of potassium channel.

关 键 词：三氧化二砷 QT间期 KV LQT1 GERG 

分 类 号：R-33[医药卫生] R54