论文部分内容阅读
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 (2 0 μg·kg 1·d 1)与地高辛 (32 μg·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 0mmHgvs 115 7± 8 2mmHg ,P <0 0 1) ,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。
Objective To compare the effects of ouabain and digoxin on the expression of Na +, K + ATPase subunit genes in rat myocardium and to explore the biological effects of endogenous ouabain (EO) The molecular mechanism of action. Methods Rats were injected with low dose ouabain (20 μg · kg · d 1) and digoxin (32 μg · kg · d 1) every day, and the blood pressure of rats was measured once a week. Animals were sacrificed after 6 weeks RT-PCR was used to detect the gene expression changes of α1, α2 and α3 subunits of sodium pump in rat myocardium at mRNA level. Results The blood pressure of ouabain was significantly increased in 6 weeks after injection of ouabain (132 6 ± 90 mmHg vs 115 7 ± 82 mmHg, P <0.01). However, there was no significant difference in blood pressure between digoxin group and control group. Both ouabain and digoxin could result in changes of gene expression of sodium pump α subunit in rat myocardium: both of them could induce the increase of α3 subunit of sodium pump, but had no effect on the expression of α2 subunit; The expression of α1 subunit of rat cardiac pump decreased, while the expression of α1 subunit of digoxin group did not change. Conclusions ouabain and digoxin lead to different changes of sodium pump gene expression, which may be one of the molecular mechanisms of endogenous ouabain playing a physiological role, and may be ouabain and digoxin pharmacology and toxicology Role (including the two on the regulation of blood pressure) different important reasons.