孕期尼古丁暴露对子代神经和智力发育的影响.docVIP

 孕期尼古丁暴露对子代神经和智力发育的 影响# 朱晓楠，鄢友娥，金浩，王纯弈，贾海珍，冯莹，汪晖** 5 10 （武汉大学基础医学院药理学系，武汉 430071） 摘要：目的：研究孕期尼古丁暴露对幼鼠神经和智力发育的影响。方法：建立孕期尼古丁暴 露所致小鼠胎儿宫内发育迟缓(IUGR)模型，观察孕期母鼠体重改变，胎鼠出生体重、大脑 皮层重和海马形态结构。测定小鼠生长发育过程中神经发育指标、运动和协调能力、自主活 动能力和学习记忆功能。结果：与正常对照组相比，尼古丁处理组孕鼠体重增长和大脑皮层 重均显著降低(P 0.05,P 0.01)；海马区细胞结构异常；仔鼠早期反射时间明显延长(P 0.05,P 0.01)，运动协调能力和自主活动能力显著降低(P 0.05,P 0.01)；Y-迷宫实验中学 习及记忆能力均降低(P 0.05)。结论：孕期尼古丁暴露可能影响子代的神经和智力发育。 关键词：毒理学；尼古丁；宫内发育迟缓；神经和智力发育； 中图分类号：R99 15 The effect of nicotine exposure during pregnancy on nerve and mental development ZHU Xiaonan, YAN Youe, JIN Hao, WANG Chunyi, JIA Haizhen, FENG Ying, Wang Hui 20 25 30 35 40 (Department of Pharmacology of Basic Medical College, Wuhan University, Wuhan 430071, China) Abstract: Objective: To determine whether in utero nicotine exposure induces long-term neurobehavioral and mental alterations. Methods: Gravid mice were subjected to nicotine in order to build IUGR model. Their offspring were subsequently evaluated in developmental and behavioral tests. Results: The intrauterine nicotine exposure has resulted in significant reduced postnatal body and cerebral cortex weight, abnormal cellular structure in hippocampus accompanied by reduced gestational body weight gain in their mothers. Such exposure also induced remarkable developmental delay in neonatal reflexes and notable behavioral deficit in adulthood, namely reduced motive coordination and locomotor activity as well as impaired learning and memory abilities. Conclusion: Our study shows the long-term neurotoxicity associated with prenatal nicotine exposure. Key words: Toxicology; Nicotine; intrauterine growth retardation (IUGR); nerve and mental development 0 引言 我国是世界第一吸烟大国，孕妇接触尼古丁的机会相当多。文献及本课题组前期研究表 明，孕期尼古丁暴露是导致胎儿宫内发育迟缓（intrauterine growth retardation, IUGR）的重 要原因[1]。IUGR 患儿出生后不仅体格发育落后，且常伴有脑发育的异常及智力低下[2]。但 研究表明尼古丁对神经系统功能的影响仍存在争议。有文献报道，尼古丁对帕金森病大鼠纹 状体 GDNF 表达及多巴胺含量有明显改善作用[3]，尼古丁可能通过活化尼古丁乙酰胆碱受体 （nAHhRs）和清除活性氧自由基机理预防和治疗老年神经退行性疾病[4]。然而，也有研究 基金项目：高等学校博士学科点专项科研基金资助课题（No.2008048610