ZINC NUTRITION AND ALCOHOL--EFFECT ON FETAL BRAIN

营养物质转运受损所致的胎儿营养不良被提出如下 乙醇致畸的机理(乙醇)中国人的营养 慢性酗酒者往往是次优的，如果与 胎盘功能障碍，可能会增加胎儿营养不良的可能性。 无水乙醇相关胎儿畸形与胎盘发育异常的相似性 妊娠期锌缺乏症的神经病理学已被公认 之前。由于慢性锌缺乏症的普遍存在 酗酒者，可以合理地检验母体乙醇 摄入，再加上限制锌的摄入量，可能会严重抑制 胎盘锌转运，导致胎儿缺锌，损害大脑 发展。拟议的研究将通过测量来探索这些概念 65锌转运，胎盘血流，母体和胎儿组织锌水平， 以及乙醇暴露后成人大脑皮质的微化学构筑 宫内缺锌。 怀孕的大鼠将暴露在短期限锌和乙醇中 在两个胎龄[10-12天(神经母细胞增殖)或天数 18-20(神经元迁移)]或饲喂不同锌/乙醇比的流食 整个孕期的构图。随意或成对饲喂补锌 控制组将接受乙醇的等卡路里碳水化合物替代。锌 代谢将通过：a)胎盘对~(65)Zn的转运和摄取。 胎儿脑组织和其他组织和b)锌池大小。母体和胎儿锌 状态将与同一动物的胎盘血流量有关 57Co标记微球。妊娠结局将由以下因素决定 检查胎儿体重、吸收和大体畸形。如果 乙醇/锌缺乏会干扰神经元的增殖或迁移， 然后，可能会在成年大脑皮质检测到特定的生化变化。我 建议分析这些大鼠的DNA，神经节苷脂(突触标志物)， 神经节苷脂和半乳脑苷脂(一种髓鞘)的分布 标记)在皮质板中使用的微量化学技术 并将这些测量结果与锌的状况和 胎盘血流。乙醇和锌限制相互作用的研究 抑制胎盘锌引起脑组织生化改变 运输支持与Etoh相关的胎儿 异常是由胎儿营养不良引起的。这样的观察将会 为慢性酒精中毒的膳食补充提供更大的动力 帮助母亲减轻孕期乙醇的潜在毒性作用。

Fetal malnutrition due to impaired nutrient transport has been proposed as a mechanism for the teratogenicity of ethanol (EtOH). The nutrition of chronic alcoholics is frequently suboptimal which, if associated with placental dysfunction, may increase the potential for fetal malnutrition. The similarity between EtOH-associated fetal abnormalities and the neuropathology of gestational zinc (Zn) deficiency has been recognized previously. Because of the prevalence of Zn deficiency in chronic alcoholics, it is reasonable to test the hypothesis that maternal EtOH ingestion, coupled with restricted Zn intake, may critically depress placental Zn transport, induce fetal Zn deficiency, and impair brain development. The proposed studies will explore these concepts by measuring 65Zn transport, placental blood flow, maternal and fetal tissue Zn levels, and the microchemical architecture of adult cortex after exposure to EtOH and Zn deficiency in utero. Pregnant rats will be exposed to either short-term Zn restriction and EtOH during 2 gestational ages [days 10-12 (neuroblast proliferation) or days 18-20 (neuronal migration)] OR fed liquid diets of varying Zn/EtOH composition throughout gestation. Ad libitum or pair-fed Zn-supplemented controls will receive isocaloric carbohydrate substitution for EtOH. Zn metabolism will be assessed by: a) placental 65Zn transport and uptake by fetal brain and other tissues and b) Zn pool size. Maternal and fetal Zn status will be related to placental blood flow in the same animal using the 57Co-labeled microspheres. Pregnancy outcome will be determined by examining the fetal weight, resorptions, and gross malformation. If EtOH/Zn deficiency interferes with neuronal proliferation or migration, then specific biochemical changes may be detected in adult cortex. I propose to analyze such rats for DNA, ganglioside (a synaptic marker), distribution of ganglioside species, and galactocerebroside (a myelin marker) in cortical laminae employing microchemical techniques used previously by myself and correlate these measurements with Zn status and placental blood flow. Demonstrating that EtOH and Zn restriction interact to produce biochemical changes in brain by inhibiting placental Zn transport would support the hypothesis that EtOH-associated fetal abnormalities result from fetal malnutrition. Such observations would provide a greater impetus for dietary supplementation of chronic alcoholic mothers to ameliorate the potential toxic effects of EtOH during gestation.