产前应用地塞米松对早产仔鼠脑发育的影响

Influences of antenatal administration of dexamethasone on brain development of premature offsprings in SD rats

目的探讨产前孕鼠使用地塞米松不同次数对早产仔鼠脑发育的影响。方法孕SD大鼠分为产前地塞米松3剂组（3只）：于妊娠第16、17、18天给予地塞米松0．8mg／（kg·d）生理盐水稀释至4m1腹腔注射；地塞米松1剂组（3只）：于妊娠第16、17天腹腔注射4ml生理盐水，第18天腹腔注射等体积的地塞米松0．8mg／（kg·d）；对照组（3只）：于妊娠第16、17、18天各腹腔注射生理盐水4m1。孕19d处死大鼠，取仔鼠称体重及脑重，免疫组织化学法检测脑组织特异性烯醇化酶（NSE）表达，电镜观察脑超微结构。组间差异比较采用ANOVA。结果（1）地塞米松3剂组体重、脑重、脑重／体重分别为（1．543±0．052）g、（88．80±7．12）mg和（5．75±0．38）％，1剂组分别为（1．584±0．035）g、（98．21±3．71）mg和（6．20±0．26）％，均低于对照组[（1.696±0．076）g、（111．53±6．29）mg和（6．59±0．48）％]（P〈0．01或P〈O．05）；且地塞米松3剂组低于1剂组（P〈0．01或P〈0．05）。（2）地塞米松3剂组脑皮质及海马区NSE表达强度分别为0．223±0．054和0．192±0．054，1剂组分别为0．381±0．041和0．359±0．046，均低于对照组（0．590±0．064和0．529±0．068）（P均〈0．01）。（3）地塞米松组早产仔鼠脑超微结构可见神经元核膜断裂、线粒体空泡变性、核仁消失、神经纤维丝断裂。结论产前使用地塞米松可损伤早产仔鼠脑发育，且多次使用比单次使用对脑组织的损伤更大。

Objective To explore the effects of different courses of antenatal dexamethasone on brain development of premature SD rats. Methods The pregnant rats were randomly assigned to 3 groups： 3- dose dexamethasone （group 1）, 1-dose dexamethasone group （group 2） and control group. The treated pregnant rats received 0.8 mg/（kg · d） of dexamethasone intraperitoneally at each time. The pregnant rats were sacrificed on 19 days of gestation, body and whole brain weight of the offspring rats were measured. Meanwhile the expression of neuron specific enolase （NSE） in brains of offspring rats was detected by immunohistochemical staining. The histological structures of baby rat brain were observed under transmission electron microscope. The differences among the three groups were analyzed by ANOVA. Results （1） The body and whole brain weight, the brain and body weight ratio were （1. 543±0. 052） g, （88.80±7.12） rag, and （5.75±0. 38）% in group 1 and （1. 584±0. 035） g,（98.21±3.71） mg, and （6.20±0. 26）% in group 2, both were lower than the control group [（l. 696±0.076） g, （111.53±6.29） mg, （6.59±0.48） %], （P〈0. 01 or P〈0. 05, respectively）. （2） The expression of NSE in cortex in group 1 and 2 were lower than that in control group （0. 223±0. 054, 0. 381±0. 041 vs 0. 590±0. 064） （P〈0. 0l）. The expression of NSE in hippocampi in group 1 and 2 were also lower than that in the control group （0. 192±0. 054, 0. 359 ±0.046 vs 0.529 ± 0.068） （P〈0.01）. （3） Disconnection of nuclei membrane, vacuolization in mitochondria, loss of nucleolus, and disconnection of neurofilaments were observed in the ultrastructure of baby rat brain tissue in both group 1 and 2. Conclusions Antenantal administration of dexamethasone can cause impairment of brain development in premature offspring rats and this might be related to the times of dexamethasone administered.