地塞米松产前应用对新生大鼠皮层神经元惊厥损伤后GR表达的影响

摘要

Objective To observe the effects of prenatal application of dexamethasone (DEX) on the expression of glucocorticoid receptor (GR) in cortical neurons of neonatal rats after magnesium-free induction of seizures,and to investigate the protective effect of glucocorticoids on neonatal cortical neurons.Methods Twenty-four pregnant SD rats were randomly divided into three groups with 8 rats in each group,including a normal control group,the DEX group and a normal saline group (NS group).On the gestational day 16,17 and 18,rats in the DEX and NS groups were intramuscularly injected with DEX [0.5mg/(kg.d)] and normal saline (0.3 mL/d),respectively; rats in the control group without any treatment.All rats of the three groups were delivered spontaneously (term =22 d).Neonatal rats in the DEX and NS groups (except NC group) were selected to establish seizure models by Mg2+ free culture.The expression of GR mRNA and protein were detected by real-time PCR and immunocytochemistry staining at 1 d,7 d and 12 d after transient Mg2+free treatment.Results Compared with the control group,the expression of GR in the DEX and NS groups was increased at 1 d and 7 d after transient Mg2 + free treatment (all P ＜ 0.05),but decreased significantly at 12 d (all P ＜ 0.05) ; compared with the NS group,the expression of GR in cortical neurons of the DEX group was decreased significantly at 1 d,7 d and 12 d (all P ＜ 0.05).Conclusion Prenatal one-way application of small dose of DEX can down-regulate the GR expression in the cerebral cortical neurons of neonatal rats after seizures,which provides a new idea for the prevention and treatment of neonatal brain injury.%目的 观察产前使用地塞米松(DEX)对新生大鼠大脑皮层神经元无镁(Mg2+)诱导惊厥后糖皮质激素受体(GR)表达的影响,探讨糖皮质激素对新生儿大脑皮层神经元的保护作用.方法 将大鼠分为正常对照组、产前DEX干预组(DEX组)、产前生理盐水干预组(NS组),在孕16、17、18d,DEX组肌注DEX 0.5 mg/(kg·d),NS组肌注生理盐水0.3 mL/d,正常对照组不予处理.所有孕鼠自然分娩后,每组按随机数字表法抽取8只新生鼠,取皮层神经组织进行皮层神经元体外培养.DEX组及NS组大脑皮层神经元给予无Mg2+培养以诱导惊厥损伤,正常对照组不予处理.在无Mg2损害后第1、7、12天,应用免疫细胞化学法及实时荧光定量PCR法检测各组皮层神经元GR的表达情况.结果 与正常对照组比较,DEX组和NS组皮层神经元在无Mg2+损伤后第1、7天GR表达增高(P均＜0.05),但第12天GR表达均下降(P均＜0.05)；与NS组比较,DEX组皮层神经元在损伤后第1、7、12天,GR表达均降低(P均＜0.05).结论 小剂量DEX产前单程使用可降低新生鼠大脑皮层神经元在发生惊厥损害后的GR表达,可为新生儿脑损伤的防治提供新的思路.