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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。
Objective To compare the effects of ouabain and digoxin on the expression of Na +, K + ATPase α subunit gene in rats, and to explore the biological effects of endogenous ouabain (EO) The molecular mechanism of pharmacological effects. Methods Rats were injected with ouabain (20 μg · kg-1 · d-1) and digoxin (32 μg · kg-1 · d-1) for a long time to observe the changes of blood pressure in rats. Molecular biology RT-PCR and immunohistochemical techniques to explore the changes of mRNA and protein expression of α1, α2 and α3 subunits of pituitary sodium pump in rats in each group. Results Ouabain and digoxin on blood pressure in rats there is a significant difference in the long-term administration of small doses of ouabain can rat blood pressure, while digoxin has no effect on blood pressure in rats. The effects of ouabain and digoxin on the expression of pituitary sodium pump α subunit were significantly different: at mRNA level, ouabain significantly decreased the expression of α1, α2 and α3 subunits, while digoxin induced only α3 subunit At the protein level, ouabain attenuated the expression of α2 and α3 subunits and did not change the α1 subunit. However, the expression of α1 and α3 subunits was attenuated by digoxin, while the α2 subunit was unchanged. Conclusion ouabain may play an important role in the pathogenesis of hypertension; ouabain and digoxin may lead to different changes of sodium pump gene expression. To further reveal the physiological and pathological effects of EO and the pharmacological and toxicological effects of digitalis drugs The molecular mechanism provides a theoretical and experimental basis.