【摘要】 目的　对比研究哇巴因与地高辛对大鼠垂体钠泵(Na+,K+ ATP酶 )α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　长期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) ,动态观察大鼠血压变化 ;分别应用分子生物学RT PCR及免疫组织化学技术 ,探讨各组大鼠垂体钠泵α1、α2 及α3 亚单位mRNA及蛋白水平基因表达的改变。结果　哇巴因与地高辛对大鼠血压的影响存在着明显差别 ,长期给予大鼠注射小剂量哇巴因可使大鼠血压升高 ,而地高辛对大鼠血压无影响。哇巴因与地高辛对垂体钠泵α亚单位表达的影响存在明显不同 :在mRNA水平 ,哇巴因使α1、α2 及α3 亚单位的表达均明显减弱 ,而地高辛仅使α3 亚单位表达减弱 ;在蛋白水平 ,哇巴因使α2 及α3 亚单位表达减弱 ,α1亚单位无改变 ,而地高辛使α1及α3 亚单位表达减弱 ,α2 亚单位无改变。结论　哇巴因在高血压发病中可能起着重要作用 ;哇巴因与地高辛可导致不同的钠泵基因表达改变 ,为进一步揭示EO生理与病理作用以及洋地黄类药物药理与毒理作用的分子机制提供了理论及实验依据。更多还原

【Abstract】 AIM To compare the effects of ouabain and digoxin on both the systolic blood pressure (SBP) and sodium pump α subunit expression in the pituitary of rats. METHODS Normal Sprague Dawley (SD) rats were injected with ouabain, digoxin and normal saline (NS), respectively, everyday and indirect SBP were recorded once a week. Six weeks later, all the rats were killed and sodium pump α 1 , α 2 , and α 3 subunit were detected in the pituitary with RT PCR method and immunohistochemical assay at mRNA and protein levels, respectively. RESULTS SBP of rats infused with ouabain increased significantly at the end of week 6 (132 6±9 0 vs 115 7±8 2 mmHg, P <0 01), while no difference of SBP was found between digoxin group and NS group. The effects of ouabain and digoxin on sodium pump α subunit isoform expression in pituitary were also different: At mRNA level, all the three isoforms of sodium pump decreased in ouabain group but only α 3 subunit decreased in digoxin group. At protein level, the α 2 and α 3 subunit decreased and α 1 subunit unchanged in ouabain group, while the α 1 and α 3 subunit decreased and α 2 subunit unchanged in digoxin group. CONCLUSION Those results suggested that both ouabain and digoxin could regulate the sodium pump α subunit isoform expression, which might be related to the physiological roles of endogenous ouabain and responsible for the difference between the pharmacological and toxicological effects of ouabain and digoxin, including their effects on blood pressure.更多还原