目的 对比研究哇巴因与地高辛对大鼠心肌钠泵(Na+-K+-ATP酶)α亚单位基因表达的影响。方法 长期给予大鼠注射小剂量哇巴因(20 μg*kg-1*d-1)与地高辛(32 μg*kg-1*d-1)，分别应用分子生物学RT-PCR及免疫组织化学技术分析大鼠心肌钠泵α1、α2及α3亚单位mRNA及蛋白水平基因表达的改变。结果 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。无论是在mRNA水平还是在蛋白水平，哇巴因组大鼠心肌钠泵α1亚单位表达减弱，α3亚单位表达增强，而α2亚单位表达无改变；地高辛组大鼠心肌钠泵α3亚单位表达增强，而α1与α2亚单位表达无改变。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。%Objective To compare the effects of ouabain and digoxin on both the systolic blood pressure (SBP) and sodium pump α-subunit expression in myocardium of rats. Methods Normal Sprague-Dawley (SD) rats were injected with ouabain, digoxin or normal saline (NS) everyday and indirect SBP was recorded once a week. Six weeks later, all the rats were killed and sodium pump α1-, α2-, and α3-subunit were detected in the left ventricular myocardium with RT-PCR method and immunohistochemical assay at mRNA and protein levels. Results At the end of six weeks SBP of rats infused with ouabain increased significantly (132.6±9.0 vs 115.7±8.2 mm Hg， 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 myocardium were also different: both ouabain and digoxin stimulated expression of α3-isoform whereas α2-isoform unchanged at both mRNA and protein levels. α1-isoform was decreased in ouabain group and α1-isoform unchanged in digoxin group at both mRNA and protein levels. Conclusion It is suggested 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 between the pharmacological and toxicological effects of ouabain and digoxin, including their effects on blood pressure.
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