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目的研究氟哌啶醇对兔左心室肌细胞钾通道基因水平的影响,探讨氟哌啶醇致心律失常的分子机制。方法实验组分别耳缘静脉注射氟哌啶醇(Haloperidol,Hal)1,2,4mg.kg-1.d-1,假手术组注射2ml.d-1生理盐水,同时监测心电图。应用逆转录-聚合酶链反应技术(RT-PCR),对ERG、KvLQT1和mink的基因表达进行半定量分析。结果氟哌啶醇低、中、高剂量组KvLQT1、mink及ERG mRNA表达较正常组降低(P<0.05),假手术组与正常组差异无统计学意义(P>0.05)。结论氟哌啶醇可能通过降低IKr、IKs钾通道基因KvLQT1、mink及ERG的表达,而使钾离子外流减少,心肌细胞动作电位时程延长,增加QT间期延长诱发Tdp的风险。
Objective To investigate the effect of haloperidol on the gene expression of potassium channel in left ventricular myocytes of rabbits and to explore the molecular mechanism of haloperidol-induced arrhythmia. Methods The rabbits in the experimental group were injected Haloperidol (Hal) 1, 2 and 4 mg.kg-1.d-1 respectively. The sham-operation group was injected with 2ml.d-1 normal saline and the electrocardiogram was monitored. Semi-quantitative analysis of the gene expression of ERG, KvLQT1 and mink was performed using reverse transcription-polymerase chain reaction (RT-PCR). Results The expressions of KvLQT1, mink and ERG mRNA in low, middle and high dose haloperidol group were lower than those in normal group (P <0.05). There was no significant difference between sham operation group and normal group (P> 0.05). Conclusions Haloperidol may decrease the outflow of potassium ions and prolong the action potential duration of cardiomyocytes by decreasing the expressions of KvLQT1, mink and ERG in potassium channels of IKr and IKs, and increase the risk of Tdp induced by QT prolongation.