哇巴因与地高辛对大鼠肝脏钠泵A亚单位基因表达的影响  

Differential regulation of sodium pump A-subunit isoform gene by ouabain and digoxin in rat liver

作　　者：原卫清[1] 王颢[1] 吕卓人[1] 

机构地区：[1]西安交通大学第一医院心脏内科,陕西西安710061

出　　处：《第四军医大学学报》2001年第16期1451-1455,共5页Journal of the Fourth Military Medical University

基　　金：国家自然科学基金资助项目 (3 96 70 3 2 5 )

摘　　要：目的　观察哇巴因与地高辛对大鼠肝脏钠泵基因表达的影响 .方法　分别给大鼠注射哇巴因 (2 0 μg· kg- 1·d- 1 )、地高辛 (32 μg·kg- 1·d- 1 )和生理盐水 (1m L· kg- 1·d- 1 ) ,观察给药后 6wk大鼠血压的动态变化 ;并分别应用分子生物学 RT- PCR及免疫组织化学技术 ,探讨各组大鼠肝脏钠泵 α1 ,α2 及 α3 亚单位 m RNA及蛋白水平基因表达的改变 .结果　给予哇巴因 2 wk后大鼠血压开始升高 ,至 6 wk时明显高于生理盐水组 (17.7± 1.2 ) vs(15 .4± 1.1) k Pa,P<0 .0 1) ,而实验过程中地高辛组血压与对照组比较差异不明显 .无论是在 m RNA水平还是在蛋白水平 ,哇巴因对大鼠肝脏钠泵α1 亚单位表达无影响 ,而地高辛使α1 亚单位表达增强 ;两组大鼠 α2 亚单位表达均无改变 ;哇巴因使 α3 亚单位蛋白水平表达减弱 ,而 m RNA水平增强 ,地高辛组大鼠肝脏钠泵 α3 亚单位无论在 m RNA水平及蛋白水平表达均增强 .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 。AIM To study the differential regulation of sodi um pump α subunit isoform gene by ouabain and digoxin in rat livers. METHODS Effects of ouabain and digoxin on both systolic blood pressure (SBP) and sodium pump α subunit expression in rat liver were compared. Normal Spraque Dawley (SD) rats were injected with ouabain (20 μg· kg -1 ·d -1 ), digoxin(32 μg·kg -1 ·d -1 ) and normal saline (NS, 1 mL· kg -1 ·d -1 )) every day respectively, and indirect SBP was recorded once a week. Six weeks later, all the rats were sacrificed and sodium pump α 1 , α 2 , and α 3 subunit were detected in the liver with RT PCR method and immunohistochemical assay at both mRNA and protein levels, respectively. RESULTS SBP of rats infused with ouabain increased significantly after 6 weeks (17.7±1.2) vs (15.4± 1.1) kPa, P <0.01, while no difference of SBP was found between digoxin group and NS group. The α 1 subunit was unchanged in ouabain group and increased in digoxin group both at mRNA and protein levels. The α 2 was unchanged in both groups. Ouabain decreased α 3 subunit expression at protein level but increased at mRNA level. Digoxin stimulated α 3 expression both at protein and mRNA level. CONCLUSION 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.

关 键 词：哇巴因 地高辛 肝 Na(+)-K(+)-交换ATP酶 高血压 基因表达 

分 类 号：R544.1[医药卫生—心血管疾病]