产前孕鼠应用地塞米松与倍他米松对早产仔鼠脑发育的影响

Effects of Antenatal Dexamethasone and Betamethasone Application in Pregnant Rats on Development of Brain in Offspring Premature Rats

目的比较产前孕鼠使用地塞米松、倍他米松对早产仔鼠脑发育的影响。方法取15只孕鼠随机分为5组:地塞米松1剂组[0.2mg/(kg.d),1d]、地塞米松3剂组[0.2mg/(kg.d),3d]、倍他米松1剂组[0.2mg/(kg.d),1d]、倍他米松3剂组[0.2mg/(kg.d),3d]及对照组。于孕第19天处死大鼠,取早产仔鼠称其体质量及脑质量,应用免疫组织化学检测其脑神经元特异性烯醇化酶(NSE)表达情况。结果地塞米松1剂组、地塞米松2剂组及倍他米松3剂组早产仔鼠体质量、脑质量、脑质量/体质量、脑皮质及海马区NSE表达均较对照组显著降低(Pa<0.05,0.01)。与地塞米松1剂组、倍他米松1剂组比较,地塞米松3剂组、倍他米松3剂组对早产仔鼠脑发育影响更大;地塞米松3剂组海马区NSE表达较倍他米松3剂组低(P<0.05),地塞米松1剂组仔鼠体质量、脑质量、脑质量/体质量、脑皮质及海马区的NSE表达均较倍他米松1剂组明显降低(Pa<0.05,0.01)。结论产前应用糖皮质激素可损伤早产仔鼠脑发育,多次使用比单次使用更加明显;而倍他米松相对地塞米松而言,对仔鼠脑发育的影响小,临床应考虑使用低毒性的倍他米松替代地塞米松。

Objective To compare the effects of antenatal Dexamethasone and Betamethasone application in pregnant rats on development of brain in offspring premature rats. Methods Fifteen pregnant rats were randomly assigned to 5 groups （ n = 3 ） ： 1 - day Dexamethasone and Betamethasone group[0.2 mg/（kg · d）, 1 d] ,3 -day Dexamethasone and Betamethasone group[0.2 mg/（ kg · d）,3 d] and control group. The body and whole brain weight of offspring rats from pregnant rats being killed in different groups were examined on the 19^th day of embryo. Meanwhile the expression of neuron specific enolase （NSE） in brain of offspring rat was measured by immunohistochemical staining. Results Compared with control group,the body and whole brain weight,the ratio of the brain and the body weight,the expression of NSE of fetal rat in cortex and hippocampi were significantly decreased in the Dexamethasone and Betamethasone treatment groups except in I - day betamethasone group（ P 〈0.05,0.01 ）. The offspring premature rats showed stronger impairment on brain development in 3 -day Dexamethasone or Betamethasone groups than that in 1 - day Dexamethasone or Betamethasone group,correspondingly. Compared with 3 - day Betamethasone group,the expression of NSE of fetal rat in hippocampi was significantly decreased in 3 -day Dexamethasone group（ P 〈 0.05 ）. The body and whole brain weight, the ratio of the brain and the body weight, the expression of NSE of fetal rat in cortex and hippocampi significantly decreased in 1 -day Dexamethasone group compared with 1 -day Betamethasone group（ Pa 〈 0.05,0.01 ）. Conclusions Antenatal administration of corticosteroid can cause impairment of brain development in offspring premature rats. The impairment of corticosteroid on brain was related to the doses. Compared with Dexamethasone, Betamethasone has slighter effect on brain development. Application of low toxic Betamethasone as the substitution of Dexamethasone should be considered in clinic.