首页> 中文期刊> 《中华医学杂志(英文版)》 >哇巴因与地高辛对大鼠心肌钠泵α亚单位基因表达影响的对比研究

哇巴因与地高辛对大鼠心肌钠泵α亚单位基因表达影响的对比研究

         

摘要

Objective To compare the effects of ouabain and digoxin on the gene expression of sodium pump rnα-subunit isoforms in the myocardium of rats.rnMethods Normal Sprague-Dawley (SD) rats were injected with ouabain (20 μg· kg-1· d-1, i.p. ), digoxin rn(32 μg· kg-1· d-1, i.p. ) and normal saline (NS) once a day, respectively, and indirect systolic blood rnpressure was recorded once a week. Six weeks later, all of the rats were killed, and sodium pump α1-,rnα2-, and α3-subunit mRNA levels in the myocardium were detected with the reverse transcription polymerase rnchain reaction (RT-PCR) method.rnResults The systolic blood pressure of the rats infused with ouabain increased significantly at the end of rnweek 6 ( 132.6 ± 9.0 mm Hg vs 115.7 ± 8.2 mm Hg, P < 0.01 ), while no difference in blood pressure was rnfound between the digoxin group and the NS group. The expression of sodium pump α-subunit isoforms in rnthe ventricular myocardium was regulated by either ouabain or digoxin. Both ouabain and digoxin stimulated rnexpression of the α3-isoform, whereas o2 was uncharcged in those two groups. α1-isoform expression rndecreased in the ouabain group and was unchanged in the digoxin group.rnConclusions These results suggest that both ouabain and digoxin could regulate sodium pump α-subunit rnisoform expression, which might be related to the physiological roles of endogenous ouabain and might be rnresponsible for the difference in the pharmacological and toxicological effects of ouabain and digoxin,rnincluding their effects on blood pressure.%目的对比研究哇巴因与地高辛对大鼠心肌钠泵(Na+,K+-ATP酶)亚单位基因表达的影响,探讨内源性rn哇巴因(EO)的生物学效应以及洋地黄类药物药理作用的分子机制。rn方法每天给予大鼠注射小剂量哇巴因(20μg·kg-1·d-1)与地高辛(32μg·kg-1·d-1),每周测量一次大鼠血rn压;6周后处死动物,应用RT-PCR技术在mRNA水平探讨大鼠心肌钠泵α1、α2及α3亚单位基因表达的改rn变。rn结果给予大鼠注射哇巴因6周后血压明显升高(132.6±9.0 mm Hg vs115.7±8.2 mm Hg,P<0.01),而rn地高辛组大鼠血压与对照组比较无明显差异。哇巴因与地高辛均可导致大鼠心肌钠泵α亚单位基因表达rn的改变:两者均可引起钠泵α3亚单位表达增强,而对α2亚单位表达无影响;哇巴因组大鼠心肌钠泵α1亚rn单位表达减弱,而地高辛组α1亚单位表达无改变。rn结论哇巴因与地高辛可导致不同的钠泵基因表达改变,这可能是内源性哇巴因发挥生理作用的分子机rn制之一,并且可能是哇巴因与地高辛药理及毒理作用(包括两者对血压的调节)不同的重要原因。

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