CAJ | 학술논문

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。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变。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亚单位表达减弱，而地高辛组α1亚单位表达无改变。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。
목적대비연구왜파인여지고신대대서심기납빙(Na+，K+-ATP매)아단위기인표체적영향，탐토내원성 왜파인(EO)적생물학효응이급양지황류약물약리작용적분자궤제。 방법매천급여대서주사소제량왜파인(20μg·kg-1·d-1)여지고신(32μg·kg-1·d-1)，매주측량일차대서혈 압；6주후처사동물，응용RT-PCR기술재mRNA수평탐토대서심기납빙α1、α2급α3아단위기인표체적개 변。 결과급여대서주사왜파인6주후혈압명현승고(132.6±9.0 mm Hg vs115.7±8.2 mm Hg，P＜0.01)，이 지고신조대서혈압여대조조비교무명현차이。왜파인여지고신균가도치대서심기납빙α아단위기인표체 적개변：량자균가인기납빙α3아단위표체증강，이대α2아단위표체무영향；왜파인조대서심기납빙α1아 단위표체감약，이지고신조α1아단위표체무개변。 결론왜파인여지고신가도치불동적납빙기인표체개변，저가능시내원성왜파인발휘생리작용적분자궤 제지일，병차가능시왜파인여지고신약리급독리작용(포괄량자대혈압적조절)불동적중요원인。
Objective To compare the effects of ouabain and digoxin on the gene expression of sodium pump α-subunit isoforms in the myocardium of rats. Methods Normal Sprague-Dawley (SD) rats were injected with ouabain (20 μg· kg-1· d-1, i.p. ), digoxin (32 μg· kg-1· d-1, i.p. ) and normal saline (NS) once a day, respectively, and indirect systolic blood pressure was recorded once a week. Six weeks later, all of the rats were killed, and sodium pump α1-, α2-, and α3-subunit mRNA levels in the myocardium were detected with the reverse transcription polymerase chain reaction (RT-PCR) method. Results The systolic blood pressure of the rats infused with ouabain increased significantly at the end of week 6 ( 132.6 ± 9.0 mm Hg vs 115.7 ± 8.2 mm Hg, P ＜ 0.01 ), while no difference in blood pressure was found between the digoxin group and the NS group. The expression of sodium pump α-subunit isoforms in the ventricular myocardium was regulated by either ouabain or digoxin. Both ouabain and digoxin stimulated expression of the α3-isoform, whereas o2 was uncharcged in those two groups. α1-isoform expression decreased in the ouabain group and was unchanged in the digoxin group. Conclusions These results suggest that both ouabain and digoxin could regulate sodium pump α-subunit isoform expression, which might be related to the physiological roles of endogenous ouabain and might be responsible for the difference in the pharmacological and toxicological effects of ouabain and digoxin, including their effects on blood pressure.