目的了解胚胎期开始的边缘缺乏(MVAD)对幼鼠海马神经元的形态及功能造成的损害,以及从新生儿期开始维生素A干预,能否使这种损害得以恢复。方法 11只健康母鼠于交配前3 w开始喂饲含VA 400 IU/kg的MVAD饲料,随机抽取其子鼠19只于断乳后继续喂饲同样的MVAD饲料为VAD组。另外随机抽取13只子鼠于出生0 d开始喂饲其母鼠含VA 6500 IU/kg的正常饲料,断乳后继续饲正常饲料为干预(VAI)组。随机抽取7只健康母鼠的10只子鼠作为正常对照(control,C)组,其饲料为含VA 6500 IU/kg的正常饲料。各组幼鼠均于7 w龄处死。用高效液相色谱法(HPLC)检测血清VA浓度。对海马切片进行HE染色,了解其神经元形态及细胞核大小的改变。运用电生理技术检测幼鼠离体海马脑片CA1区长时程增强(LTP),并在VAD组人工脑脊液(ACSF)中直接加入视黄酸(RA)后检测LTP。用透射电镜观察强直刺激前后,海马CA1区突触超微结构的变化。结果 MVAD孕鼠交配时血清VA浓度明显低于对照组。VAD组血清VA浓度明显低于C组,VAI组的血清VA浓度低于C组水平,但明显高于VAD组。海马CA1区锥体细胞层神经元细胞核的面积,VAD组明显小于C组,VAI组大于VAD组,与C组比较无明显差别。C组海马CA1区群峰电位增长幅度明显大于VAD组,VAI组小于C组,大于VAD组(P<0.05);VAD组脑片的ASCF中加入RA,其群峰电位增长幅度由(22.86±3.26)%上升到(59.08±7.22)%(P<0.01),与C组无显著差异。强直刺激后的C组与空白对照组(BC)比较,其海马CA1区突触的活性区长度和突触后致密物(PSD)厚度均明显增加,突触界面模拟圆半径明显减小,突触间隙宽度没有明显差异;强直刺激后,C组突触活性区长度明显大于VAD组,与VAD+RA组比较无显著差异,C组和VAD+RA组的突触界面模拟圆半径小于VAD组。结论 MVAD可导致少量CA1区神经元缺失和坏死,并减小了海马神经元细胞核的面积。同时直接影响海马神经元LTP的诱发,以及减小了LTP诱发后突触超微结构变化的程度。新生儿期开始的VAI可使MVAD对海马神经元的影响得到部分恢复。 Objective To understand the damage caused by the lack of marginal embryo (MVAD) on the morphology and function of hippocampal neurons and the intervention of vitamin A from neonatal period to restore this damage. Methods Eleven healthy mothers were fed with MVAD diet containing 400 IU / kg of VA at 3 w before mating and 19 offspring were randomly selected to receive the same MVAD diet for the VAD group after weaning. Thirteen other offspring were randomly selected and fed with normal diet containing 6500 IU / kg of VA at 0 d after birth, and then fed with normal diet intervention (VAI) after weaning. Ten healthy offspring of seven healthy daughters were randomly selected as the control (C) group, and their feed was normal feed with VA of 6500 IU / kg. All pups were sacrificed at 7 weeks. Serum VA concentrations were measured by high performance liquid chromatography (HPLC). HE staining of hippocampal slices to understand the changes in neuronal morphology and nucleus size. The electrophysiological technique was used to detect the long-term potentiation (LTP) of hippocampal CA1 region in isolated rat hippocampal slices. LTP was detected by the direct addition of retinoic acid (RA) to the artificial cerebrospinal fluid (ACSF) of VAD rats. Transmission electron microscopy was used to observe the changes of synaptic ultrastructure in the hippocampus CA1 before and after the tonic stimulation. Results The MVAD of pregnant mice fed with MVAD was significantly lower than that of the control group. The concentration of serum VA in VAD group was significantly lower than that in C group, and the serum VA concentration in VAI group was lower than that in C group, but significantly higher than that in VAD group. The area of ​​pyramidal cell nuclei in hippocampal CA1 pyramidal cell layer in VAD group was significantly lower than that in C group, VAI group was larger than VAD group, there was no significant difference compared with C group. Compared with VAD group, the peak potential of hippocampal CA1 group in C group increased more significantly than that of VAD group (P <0.05), and the peak potential increased by (22.86 ± 3.26)% to (59.08 ± 7.22)% (P <0.01), no significant difference with C group. Compared with the blank control group (BC), the length of synaptic active zone and the thickness of the postsynaptic density (PSD) in hippocampal CA1 area of ​​C group were significantly increased, and the simulated radius of the synaptic interface was significantly decreased The width of synaptic cleft was not significantly different between the VAD + RA group and the VAD + RA group. The length of the synaptic active area in the C group was significantly longer than that in the VAD group . Conclusions MVAD can lead to the deletion and necrosis of a small number of neurons in CA1 area and decrease the nucleus area of ​​neurons in hippocampus. Directly affect the induction of LTP in hippocampal neurons, and reduce the degree of synaptic ultrastructure changes induced by LTP. VAI at the beginning of the neonatal period partially restored the effects of MVAD on hippocampal neurons.