Effects of neonatal dexamethasone treatment on hypothalamo-pituitary adrenal axis and immune system of the rat
Effects of neonatal dexamethasone treatment on hypothalamo-pituitary adrenal axis and immune system of the rat
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DOI：
10.1016/s0165-5728(96)00207-x
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发表时间：
1997-04-01
影响因子：
3.3
通讯作者：
vanRees, EP
中科院分区：
文献类型：
--
作者：
Bakker, JM;Schmidt, ED;vanRees, EP
合成糖皮质激素(GC)是广泛使用的药物，也用于预防早产儿发生的疾病。先前我们已经发现，孕鼠经GC治疗后，下丘脑内侧基底区AVP/CRH的比率持续增加，而新生大鼠胸腺中的CD4/CD8比率也增加。本研究的目的是调查在给予临床相关剂量的新生儿GC后是否也能看到这样的影响。地塞米松-21-磷酸(DEX；1.2微克/克体重)I.P.分别于出生后第5天和第7天给药。分别于出生后第18、33、48天检测GC对HPA轴的影响，以及对胸腺和脾中CD4(+)、CD8(+)T细胞的影响。新生儿DEX治疗在出生后第18天暂时增加(p<；0.01)AVP在正中隆起(Zeme)外区的储存，而不影响CRH的储存。在研究的任何时间间隔，新生儿DEX治疗后静息血浆ACTH和皮质酮水平保持不变。在胸腺和脾中，新生儿地塞米松治疗在出生后第18天减少(p<；0.0001)T细胞数量。此外，新生儿地塞米松治疗在出生后第18天增加了成熟的CD4(+)CD8(-)/CD4(-)CD8(+)胸腺细胞的比率(p<；0.01)，但在出生后第33天和第48天没有增加。综上所述，新生儿地塞米松治疗对下丘脑CRH神经元多肽表达和胸腺细胞成熟有暂时性影响。显然，新生儿接触GC会影响内分泌系统和免疫系统中的潜在敏感靶点，但这些变化是可逆的，并在发育过程中重新调整。
Synthetic glucocorticoids (GC) are widely used drugs, also in the prevention of diseases that occur in the preterm newborn. Previously we have found that GC treatment of pregnant rats resulted in a persistent increase in the ratio of AVP over CRH in the mediobasal hypothalamus, and in an increased CD4/CD8 ratio in the thymus of the newborn. The objective of the present study was to investigate whether such effects were also seen after neonatal GC exposure, given in clinically-relevant doses. Dexamethasone-21-phosphate (DEX; 1.2 mu g/g BW) i.p.) was given at day 5 and day 7 after birth. At day 18, 33, and 48 after birth effects of GC on the HPA-axis, and on CD4(+) and CD8(+) T cells in thymus and spleen were examined. Neonatal DEX treatment temporarily increased(p < 0.01) AVP stores in the external zone of the median eminence (ZEME) on day 18 after birth, and did not affect CRH stores. Resting plasma levels of ACTH and corticosterone remained unchanged after neonatal DEX treatment at any time interval studied. In the thymus and spleen, neonatal DEX treatment decreased(p < 0.0001)T cell numbers on day 18 after birth. Furthermore, neonatal DEX treatment increased(p < 0.01) the ratio of mature CD4(+)CD8(-) over CD4(-)CD8(+) thymocytes on day 18 after birth, but not on day 33 and day 48 after birth. In conclusion, neonatal DEX treatment has temporary effects on peptide expression in hypothalamic CRH neurons, and on thymocyte maturation. Apparently, neonatal exposure to GC affects potentially sensitive targets within the endocrine system and immune system but these alterations are reversible and readjusted during development.