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倍他米松对发育中兔肾上腺多巴胺D1受体mRNA表达的影响。

Effect of betamethasone on the expression of dopamine D1 receptor mRNA in the developing rabbit adrenal gland.

作者信息

Labaune Jean-Marc, Boutroy Marie-Jeanne, Bairam Aida

机构信息

JE 2164 Neonatal Adaptation and Development, Henri Poincaré Nancy1 University, Academic Regional Maternity Hospital, Nancy, France, and ; Unit of Research in Perinatology, Academic Hospital, Pavillon Saint François d'Assise, Laval University, Quebec, Canada.

JE 2164 Neonatal Adaptation and Development, Henri Poincaré Nancy1 University, Academic Regional Maternity Hospital, Nancy, France, and.

出版信息

Curr Ther Res Clin Exp. 2003 Sep;64(8):568-79. doi: 10.1016/j.curtheres.2003.09.009.

Abstract

BACKGROUND

Antenatal corticotherapy is widely used to enhance pulmonary fetal maturation in cases in which premature birth is likely. The adrenal gland, which has a key role in controlling fetal and neonatal adaptation, appears to be a target organ of glucocorticoids.

OBJECTIVES

The aim of this study was first to determine the ontogenic profile of dopamine D1 receptor (DA D1-R) messenger RNA (mRNA) in the rabbit. The effects of antenatal exposure to exogenous corticoids on levels of adrenal DA D1-R mRNA expression were examined.

METHODS

Pregnant rabbits free of any treatment or handling before delivery were chosen for the study of DA D1-R mRNA ontogenic profile. For the study of the antenatal exposure to exogenous corticoids, pregnant rabbits were given 2 injections of either betamethasone 0.1 mg/kg or saline 0.1 mL/kg. DA D1-R mRNA expression was determined using northern blot analysis at 4 developmental ages: fetus (at 27 days of gestation), 1 day of age, 25 days of age, and adulthood. Rabbits were allocated to their respective group (treated or untreated) depending on maternal treatment (betamethasone or saline, respectively).

RESULTS

Four pregnant rabbits were used for the ontogenic-profile group, which comprised 11 fetuses, seven 1-day-old rabbits, four 25-day-old rabbits, and 2 adults. Six other pregnant rabbits received betamethasone; 6 saline. The treated group comprised 12 fetuses, twelve 1-day-old rabbits, four 25-day-old rabbits, and 3 adults. The untreated group comprised 12 fetuses, fifteen 1-day-old rabbits, five 25-day-old rabbits, and 3 adults. DA D1-R mRNA was expressed in rabbit adrenal glands from the fetal period to adulthood and this expression was not age dependent. Moreover, antenatal corticotherapy induced a significant increase in respective DA D1-R mRNA levels of 20%, 15%, and 8% in treated fetuses, 1-day-old rabbits, and 25-day-old rabbits compared with the untreated groups (P <0.003, 0.003, and 0.005, respectively). This increase was not observed in adulthood.

CONCLUSIONS

In the rabbits in this study, DA D1-R mRNA expression in the adrenal gland began during gestation. Its expression was not age dependent but was rapidly modified by antenatal exposure to betamethasone. These corticoid-induced changes, observed until late infancy, did not occur in adulthood.

摘要

背景

产前皮质激素疗法广泛应用于早产可能性较大的病例,以促进胎儿肺成熟。肾上腺在控制胎儿和新生儿适应过程中起关键作用,似乎是糖皮质激素的靶器官。

目的

本研究的目的首先是确定家兔多巴胺D1受体(DA D1-R)信使核糖核酸(mRNA)的个体发育情况。研究产前暴露于外源性皮质激素对肾上腺DA D1-R mRNA表达水平的影响。

方法

选择分娩前未接受任何治疗或处理的孕兔来研究DA D1-R mRNA的个体发育情况。为研究产前暴露于外源性皮质激素,给孕兔注射2次,每次注射倍他米松0.1 mg/kg或生理盐水0.1 mL/kg。在4个发育阶段使用Northern印迹分析法测定DA D1-R mRNA表达:胎儿期(妊娠27天)、1日龄、25日龄和成年期。根据母兔的处理(分别为倍他米松或生理盐水)将家兔分配到各自的组(处理组或未处理组)。

结果

4只孕兔用于个体发育情况组,该组包括11只胎儿、7只1日龄家兔、4只25日龄家兔和2只成年家兔。另外6只孕兔接受倍他米松处理;6只接受生理盐水处理。处理组包括12只胎儿、12只1日龄家兔、4只25日龄家兔和3只成年家兔。未处理组包括12只胎儿、15只1日龄家兔、5只25日龄家兔和3只成年家兔。DA D1-R mRNA在胎儿期至成年期的家兔肾上腺中均有表达,且这种表达不依赖于年龄。此外,与未处理组相比,产前皮质激素疗法使处理组胎儿、1日龄家兔和25日龄家兔的DA D1-R mRNA水平分别显著升高20%、15%和8%(P分别<0.003、0.003和0.005)。成年期未观察到这种升高。

结论

在本研究的家兔中,肾上腺中DA D1-R mRNA的表达始于妊娠期。其表达不依赖于年龄,但产前暴露于倍他米松可使其迅速改变。这些皮质激素诱导的变化在婴儿晚期之前均可观察到,但成年期未出现。

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