摘要
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。
Aim To observe the effects of Haloperidol on the expression of Potassium channel genes in rabbit ventricular myocytes. Methods Before the use of drug, ECG was dynamically detected. Semi-quantitative reverse transcription polymerase chain reaction （RT-PCR） was used to estimate the changes of mRNA of KvLQT1 ,ERG,and mink genes, and GAPDH as internal control. Results There was no difference between normal group and sham group in the expression of KvLQT1, ERG, and mink genes （ P 〉 0.05 ）. mRNA level of KvLQT1, ERG, and mink genes decreased compared with that of normal group （ P 〈 0. 05 ）. Conclusion Haloperidol may prolong APD by down-regulating the expression of KvLQT1 , ERG, and mink genes, the ris reduces the outflow of potassi k of Torsades de points （Tdp um and increases ） induced by QTinterval prolongation.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2009年第6期758-761,共4页
Chinese Pharmacological Bulletin
基金
国家自然科学基金资助项目(No30460147)
新疆维吾尔自治区高校科研计划项目(NoXJEDU2005I14)
