【作者】 毛春婷；

【导师】 李廷玉；

【作者基本信息】 重庆医科大学 ， 儿科学， 2005， 博士

【摘要】 目的:了解胚胎期开始的边缘型维生素 A 缺乏(MVAD)对幼鼠学习记忆造成的损害,在不同的年龄阶段给予维生素 A 干预(VAI),这种损害的恢复程度是否存在差别。 方法:11只健康母鼠于交配前3周开始饲与含VA 400 IU/kg的MVAD饲料,其子鼠继续饲与同样的 MVAD 饲料。7 只健康母鼠的子鼠作为正常对照(control,C)组,其饲料含 VA 6500 IU/kg。MVAD 组和 control组母鼠的子鼠分为 VAD1 组、C1 组、VAD2 组、C2 组、VAD3 组、C3 组、VAD4 组和 C4 组,分别于胚胎 14 天、出生 0 天、4 周龄和 7 周龄处死。VAI1、VAI2 和 VAI3 组分别于胚胎 14 天、出生 0 天和 4 周龄停饲 MVAD饲料,改饲 control 组饲料至 7 周龄。记录子鼠体重,用高效液相色谱法(HPLC)检测血清 VA 浓度,用穿梭箱主动回避反应实验测试 7 周龄幼鼠的学习记忆功能,对脑或海马切片进行 H-E 染色、尼式体染色和硝酸银浸染,了解其形态学改变。用透射电镜观察海马 CA1 区神经元的超微结构。 结果:①血清 VA 浓度:MVAD 孕鼠交配时血清 VA 浓度明显低于对更多还原

【Abstract】 OBJECTIVE:To study if the learning and memory in young rats will be impaired due to marginal vitamin A deficiency beginning from embryonic period, and if there will be difference on the recovery after vitamin A intervention at different ages. METHODS:11 female rats fed with marginal vitamin A deficient food containing vitamin A 400 IU/kg 3 weeks before coitus, and 7 control female rats fed with normal food containing vitamin A 6500IU/kg. Their pups were kept on feeding with the same food as themselves. The MVAD and control pups were divided randomly into eight groups: VAD1, C1, VAD2, C2, VAD3 C3, VAD4 and C4 groups. They were killed at embryonic day 14, the day of birth, postnatal 4 weeks and 7 weeks, respectively. Additionally, rats fed with marginal vitamin A deficient food were divided into three vitamin A intervention groups (VAI1, VAI2 and VAI3) according to the time of changing to feed with normal food, i.e. embryonic day 14, the day of birth, and postnatal 4 weeks, respectively. Weight of all pups was recorded and serum vitamin A concentrations weredetected by HPLC. The shuttle box active avoidance test was used toindicate the rats’ ability of learning and memory. We could observe themorphology of hippocampus by haematine-eosin, Thionine andBielschowsky staining methods and observe the ultrastructure ofhippocampus by the transmission electron microscopy. RESULTS:① The serum vitamin A concentrations of marginalvitamin A deficient dams and pups were decreased. No clinicalmanifestation of vitamin A deficiency was observed. The serum vitamin Aconcentration of group VAD4 was lower than group C4 (P < 0.05), and theserum vitamin A concentrations of three vitamin A intervention groupswere lower than group C4 respectively (P < 0.05). The serum vitamin Aconcentrations of group VAI1 and VAI2 were higher than group VAD4 (P <0.05). And there had no significant difference between group VAI3 andVAD4 (P > 0.05). ② The weight of marginal vitamin A deficient youngrats were lower than the control rats of the same age (P < 0.05, exceptgroup C2 and VAD2). There had no difference about the weight among thethree vitamin A intervention groups, group C4 and group VAD4 (P >0.05). ③ The learning times of group VAD4 in the shuttle box test wasmore than group C4. The learning times of group VAI3 was more thangroup C4 (P < 0.05), and that of group VAI1 and VAI2 were more thangroup VAD4, respectively (P < 0.05). ④ A little neuron loss and redneuron were found in the hippocampal CA1 region pyramidal cell layer ofgroup VAD4. The area of nucleus in the hippocampal CA1 pyramidal celllayer of group VAD3 was smaller than group C3, but there had nosignificant difference between the two groups (P > 0.05). And that of groupVAD4 was smaller than group C4 (P < 0.05). The area of nucleus ofgroupVAI1 and VAI2 were bigger than group VAD4 (P < 0.05) and therehad no conspicuous difference when compared with group C4 (P > 0.05) respectively. The area of nucleus of group VAI3 was bigger than group VAD4 and was smaller than group C4 (P < 0.05). We found a little phenomena of Nissl bodies lysis, but the significantly abnormal of the morphology of nerve fiber was not found. By transmission electron microscopy, some swelling mitochondria existed in the neurons of group VAD4. CONCLUSIONS:①Marginal vitamin A deficiency beginning from embryonic period may impair the learning and memory in young rats. ②The impaired learning and memory would recover completely if the vitamin A intervention performed from embryonic period and the day of birth. And the recovery would not be very good if the vitamin A intervention performed from postnatal 4 weeks. ③Long term marginal vitamin A deficiency may influence the size of nucleus of hippocampal neuron and may contribute to a little neuron loss and necrosis. And it may not influence the morphology of the nerve fiber and the ultrastructure of neuron in hippocampus. PART Ⅱ MECHANISM OF THE EFFECTS OF MARGINAL VITAMIN A DEFICIENCY BEGINNING FROM EMBRYONIC PERIOD ON LEARNING AND MEMORY IN YOUNG RATS OBJECTIVE:To更多还原