DeJonge M H, Zachman R D
Department of Pediatrics, University of Wisconsin, Meriter Hospital, Madison 53715, USA.
Pediatr Res. 1995 Apr;37(4 Pt 1):418-23. doi: 10.1203/00006450-199504000-00006.
Ethanol consumption during pregnancy can cause fetal alcohol syndrome (FAS). Although the exact mechanism is unknown, nutritional alterations caused by ethanol exposure may be an etiologic factor in FAS. The congenital heart defects seen in FAS are similar to those found in vitamin A teratogenesis. Because ethanol ingestion alters vitamin A metabolism, we hypothesized that the cardiac manifestations seen in FAS result from an alteration in vitamin A metabolism or function in the developing fetus. Twenty-day gestation fetal rat hearts from ethanol-exposed and control pregnancies were analyzed for 1) levels of endogenous retinol, retinyl palmitate, and retinoic acid by quantitative HPLC; 2) binding activity levels of both retinol by cellular retinol binding protein and retinoic acid by cellular retinoic acid binding protein using specific competitive binding assays; and 3) relative abundance of cellular retinol binding protein and retinoic acid receptor alpha, beta, and gamma subtype message as expressed in mRNA. Levels of retinol and retinyl palmitate were significantly higher (p < 0.01) and the level of retinoic acid was significantly lower (p < 0.02) in the ethanol-exposed fetal hearts. Binding activity levels of cellular retinol binding protein and cellular retinoic acid binding protein were not different in the two groups. The message for retinoic acid receptor alpha (3.7 kb) was increased (p < 0.01) and the message for retinoic acid receptor beta was decreased (p < 0.05) in the ethanol-exposed hearts.(ABSTRACT TRUNCATED AT 250 WORDS)
孕期饮酒会导致胎儿酒精综合征（FAS）。尽管确切机制尚不清楚，但乙醇暴露引起的营养改变可能是FAS的一个病因。FAS中出现的先天性心脏缺陷与维生素A致畸作用中发现的缺陷相似。由于乙醇摄入会改变维生素A代谢，我们推测FAS中出现的心脏表现是由于发育中胎儿的维生素A代谢或功能改变所致。对乙醇暴露组和对照组妊娠20天的胎鼠心脏进行分析，检测：1）通过定量高效液相色谱法测定内源性视黄醇、棕榈酸视黄酯和视黄酸的水平；2）使用特异性竞争结合试验，检测细胞视黄醇结合蛋白对视黄醇的结合活性水平以及细胞视黄酸结合蛋白对视黄酸的结合活性水平；3）检测mRNA中表达的细胞视黄醇结合蛋白以及视黄酸受体α、β和γ亚型信息的相对丰度。乙醇暴露组胎鼠心脏中视黄醇和棕榈酸视黄酯的水平显著升高（p < 0.01），视黄酸水平显著降低（p < 0.02）。两组中细胞视黄醇结合蛋白和细胞视黄酸结合蛋白的结合活性水平无差异。乙醇暴露组心脏中视黄酸受体α（3.7 kb）的信息增加（p < 0.01），视黄酸受体β的信息减少（p < 0.05）。（摘要截选至250字）
