Cagen S Z, Gibson J E
J Pharmacol Exp Ther. 1979 Jul;210(1):15-21.
The purpose of this investigation was to characterize the development of hepatic excretory function in rats. Cumulative (40 min) intestinal ouabain content was lower and plasma ouabain concentrations were higher in 15-day-old rats than in 21-, 25-, 35- and 45-day-old animals and reached adult levels when rats were 35 days old. Impaired transport of ouabain in rat neonates correlated to low initial ouabain concentration in liver, which suggested that the inability of young rats to accumulate ouabain in liver may be the most important determinant for functional insufficiency. Bile duct ligation and bile salt infusion, treatments that primarily depress and enhance (respectively) excretion of sulfobromophthalein from liver into bile, markedly altered the disappearance of sulfobromophthalein from plasma of adult rats but did not appreciably affect sulfobromophthalein disappearance from blood of 15-day-old rats. The effect of bile duct ligation on ouabain transport in 15-day-old rats was also not as dramatic as the effect produced in adult rats. Hepatic uptake is rapid in adult rats and overall excretion is limited by a slower rate of transport from liver into bile. The lower rate of uptake in 15-day-old rats may limit overall transport function in young animals.
本研究的目的是描述大鼠肝脏排泄功能的发育情况。15日龄大鼠的累积(40分钟)肠道哇巴因含量低于21日龄、25日龄、35日龄和45日龄的动物,而血浆哇巴因浓度则较高,且在大鼠35日龄时达到成年水平。新生大鼠中哇巴因转运受损与肝脏中初始哇巴因浓度较低有关,这表明幼鼠无法在肝脏中蓄积哇巴因可能是功能不全的最重要决定因素。胆管结扎和胆盐输注分别主要抑制和增强从肝脏向胆汁中排泄磺溴酞钠,这显著改变了成年大鼠血浆中磺溴酞钠的消失情况,但对15日龄大鼠血液中磺溴酞钠的消失没有明显影响。胆管结扎对15日龄大鼠哇巴因转运的影响也不如对成年大鼠产生的影响显著。成年大鼠肝脏摄取迅速,总体排泄受从肝脏向胆汁转运速率较慢的限制。15日龄大鼠较低的摄取速率可能会限制幼龄动物的总体转运功能。