Molecular biological mechanisms of choline-modulated arsenic trioxide-induced electrocardiogram QT interval prolongation in guinea pig / 中国地方病学杂志

ABSTRACT

Objective To observe the therapeutic action of choline on As2O3 induced electrecardiogram (ECG)QT interval prolongation and to further explore molecular biological mechanisms.Methods 40 guinea pigs were divided into 5 groups randomly with 8 rats in each groupcontrol group intravenously injected with saline, experimental group with 0.4,0.8,1.6 ms/kg of choline and As2O3 group with 8 mg/kg choline plus 1.6 mg/kg As2O3.After a series of concentration of As2O3 was intravenously given,ECG was monitored at different time(0,10, 30,60,90,120 min),and corrected QT interval(QTc)was studied.Total RNA Wa$abstracted from the guinea pigs hearts after 6 h,and the effects of choline on altered L-type calcium channel α1c and potassium channel GPERG mRNA expression caused by As2O3 in cardiomyocytes of guinea pig were studied by the method of reverse transcription polyme,chain reaction(RT-PCR).Results In 0.8 mg/kg As2O3 group,the value of QTc at 60, 90 and 120 min respectively being 354 ±22.366± 31 and 368 ±29 waa significantly higher than that of control groups[(325±26,336 ±26 and 324 ±20)at same time] with a significant difference(P<0.05 or<0.01);the value of QTc at 90 and 120 rain was significantly higher than that of O min group(334 ±12),the difference being statistically significant(P<0.05).In 1.6 mg/kg As2O3 group,the value of QTc at 10,30,60,90 and 120 min respectively being 362±33,380±21,382±35,388±39 and 388 ±31 was significantly higher than that of control groups[(328 ±20.324 ±25,325 ±26,336±26 and 324 ±20)at same time]with a significant difference (P<0.05 or<0.01);the value of QTc at 10,30,60,90 and 120 min Was significantly higher than that of O min group(329 ±31),the difference being statistically significant(P<0.05).In choline+As2O3group,the value of qrc at 30,60,90 and 120 min was 337 ±17,341±15,344 ±22 and 343 ±19,significantly lower than that of 1.6 mg/kg As2O3 group,the difference being statistically significant(P<0.05 or<0.01).The RT-PCR results indicated that the value of L-type calcium channel α1c mRNA expression at the concentration of 1.6 mg/kg As2O3 was 1.27±0.14 vs 1.02±0.12 of control group(P<0.01),and it was 1.10 ±0.13 in choline+As2O3 group(P<0.05 Vs 1.6 mg/kg As2O3 group).The value of potassium channel GPERG mRNA expression were 1.29 ±0.11,1.22±0.12 and 1.27±0.16 at the dose of 0.4,0.8,1.6 mg/kg As2O3(P>0.05 VS 1.23±0.08 of control group).In choline+ As2O3 group,the value was 1.30±0.14(compared with 1.6 mg/kg As2O3 group,P>0.05).Conclusions Choline normalizes QTc abnormality during As2O3 application,and modulating changed calcium channel mRNA expression induced by As2O3 may be one of the mechanisms.