哇巴因与地高辛对大鼠肾上腺钠泵α亚单位基因表达影响的对比研究  

Differential regulation of sodium pump α-subunit isoform gene by ouabain and digoxin in the adrenal gland of rats

作　　者：王颢[1] 原卫清[1] 吕卓人[1] 

机构地区：[1]西安医科大学第一交通医院心内科,陕西西安710061

出　　处：《中国药学杂志》2001年第6期379-382,共4页Chinese Pharmaceutical Journal

基　　金：国家自然科学基金资助课题 !(3 9670 3 2 5 )

摘　　要：目的　对比研究哇巴因与地高辛对大鼠肾上腺钠泵 (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 ,探讨各组大鼠肾上腺钠泵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。哇巴因与地高辛对肾上腺钠泵α亚单位的影响存在明显差异 ;哇巴因使α1亚单位表达减弱 ,α3亚单位增强 ,而α2亚单位在蛋白水平表达减弱 ,mRNA水平增强 ;地高辛使α3亚单位表达增强 ,α2亚单位无改变 ,α1亚单位在蛋白水平表达减弱 ,mRNA水平增强。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 the adrenal gland 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 α1-, α2- and α3-subunit were detected in the adrenal gland with RT-PCR method and immunohistochemical assay at mRNA and protein levels, respectively. RESULTS: The SBP of the 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 adrenal gland were also different: Ouabain stimulated α3-subunit expression, while α1-subunit decreased both at mRNA and protein level. α2-subunit decreased at protein level but increased at mRNA level in ouabain group. In digoxin group, α3-subunit increased and α2-subunit unchanged at both mRNA and protein levels. α1-subunit increased at mRNA but decreased at protein level. 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 might be responsible for the difference between the pharmacological and toxicological effects of ouabain and digoxin, including their effects on blood pressure.

关 键 词：哇巴因 地高辛 肾上腺 钠泵 基因表达 Α亚单位 大鼠 

分 类 号：R972.1[医药卫生—药品] R966[医药卫生—药学]