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多药耐药相关磷蛋白(ABCB1)在豚鼠胎盘中的表达:发育变化及倍他米松的调节作用。

Multidrug resistance phosphoglycoprotein (ABCB1) expression in the guinea pig placenta: developmental changes and regulation by betamethasone.

机构信息

Department of Physiology, University of Toronto, Medical Sciences Building, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.

出版信息

Can J Physiol Pharmacol. 2009 Nov;87(11):973-8. doi: 10.1139/y09-087.

Abstract

Placental ABCB1 plays an important role in fetal protection against xenobiotics in the maternal circulation. Limited evidence indicates that glucocorticoids regulate ABCB1 expression in other tissues. Since approximately 10% of pregnant women are treated with synthetic glucocorticoids for threatened preterm labour, the effects of synthetic glucocorticoids on placental ABCB1 are important. We hypothesized that placental levels of ABCB1 are reduced in late gestation in the guinea pig and that synthetic glucocorticoids downregulate ABCB1 production. There was a significant decrease in placental Abcb1 mRNA expression in late gestation. Treatment of guinea pigs with betamethasone (1 mg/kg) on gestational days 40/41 and 50/51 resulted in a significant decrease in placental Abcb1 mRNA and protein expression. No sex differences were observed. Understanding the regulation of ABCB1 function will facilitate the development of treatment strategies for human fetal protection against maternally derived endobiotics and xenobiotics.

摘要

胎盘 ABCB1 在保护胎儿免受母体循环中外源物质的侵害方面发挥着重要作用。有限的证据表明,糖皮质激素在其他组织中调节 ABCB1 的表达。由于大约 10%的孕妇因早产威胁而接受合成糖皮质激素治疗,因此合成糖皮质激素对胎盘 ABCB1 的影响非常重要。我们假设豚鼠在妊娠晚期胎盘 ABCB1 水平降低,并且合成糖皮质激素下调 ABCB1 的产生。在妊娠晚期,胎盘 Abcb1mRNA 表达显著下降。在妊娠第 40/41 天和第 50/51 天用倍他米松(1mg/kg)治疗豚鼠,导致胎盘 Abcb1mRNA 和蛋白表达显著下降。未观察到性别差异。了解 ABCB1 功能的调节将有助于制定治疗策略,以保护人类胎儿免受母体来源的内源性和外源性物质的侵害。

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