ETHANOL METABOLISM IN PREGNANCY--ROLE OF DIET

描述（采用自申请人的摘要）：众所周知， 妇女比男子更容易受到酒精的不良影响。一个 据估计，5- 20%的美国妇女在怀孕期间饮酒。然而， 几乎没有研究检查乙醇对孕妇的影响。 我们开发了一种全肠内营养（TEN）模型， 怀孕的额外营养需求，这使得系统 研究这一时期的乙醇代谢和处置。使用10 系统中，我们做了几个重要的观察：第一，与常数 乙醇输注、血液和尿液乙醇浓度， 非妊娠雌性大鼠的周期在几乎为零和超过500 mg/dl之间， 每6天一次脉冲的频率。这是一个后果， 是由乙醇依赖性增加介导的“循环”乙醇代谢， 主要肝乙醇代谢酶，ADH类。第二，振幅 这些乙醇脉冲在怀孕的雌性大鼠中显著减少（65%） 与注入相同水平乙醇和卡路里的未交配大鼠相比， 这表明乙醇代谢在怀孕期间显著增加。 这将是保护性的，因为乙醇代谢的速率，在给定的 乙醇摄入量，决定了母亲血液中的乙醇浓度， 毒性第三，我们观察到， 显著提高了脉动乙醇浓度的幅度， 更高的水平。预计这会增加母体毒性。我们 假设乙醇代谢和清除率显著增加 在营养良好的妊娠大鼠中，由于内分泌变化， 能量摄入增加，导致肝脏ADH表达增加 第一类。此外，我们假设怀孕期间营养不良会导致 ADH依赖性乙醇代谢受损，这将导致增加 乙醇对母亲和胎儿的毒性。本提案的目标 使用TEN系统来研究乙醇、营养和 乙醇/营养相互作用对乙醇代谢和清除的影响 孕鼠与未孕鼠的鉴别及营养;内分泌; 这些影响的生化和分子机制。

DESCRIPTION (Adopted from the Applicant's Abstract): It is well known that women are more susceptible to the adverse effects of alcohol than men. An estimated 5-20 percent of American women consume alcohol during pregnancy. Yet, almost no research has examined the effects of ethanol in the pregnant mother. We have developed a total enteral nutrition (TEN) model that supports the additional nutritional demands of pregnancy and which allows the systematic study of ethanol metabolism and disposition during this period. Using the TEN system we have made several important observations: First, with constant infusion of ethanol, blood and urine ethanol concentrations of male and non-pregnant female rats cycle between almost zero and over 500 mg/dl with a frequency of one pulse every 6 days. This is the consequence of what appears to be "cyclic" ethanol metabolism mediated by ethanol-dependent increases in the major hepatic ethanol metabolizing enzyme, class ADH. Second, the amplitude of these ethanol pulses is markedly reduced (65 percent) in pregnant female rats compared to virgin rats infused the same level of ethanol and calories suggesting that ethanol metabolism is significantly increased in pregnancy. This would be protective since the rate of ethanol metabolism, at a given ethanol intake, determines the maternal blood ethanol concentrations and toxicity. Third, we have observed that undernutrition during pregnancy significantly elevates the amplitude of pulsatile ethanol concentrations to higher levels. This would be expected to increase maternal toxicity. We hypothesize that ethanol metabolism and clearance are significantly increased in the well nourished pregnant rat as a consequence of endocrine changes and increased energy intake which result in increased expression of hepatic ADH class 1. In addition, we hypothesize that undernutrition in pregnancy results in impairment of ADH-dependent ethanol metabolism, which will lead to increased ethanol toxicity to both mother and fetus. The goals of the current proposal are to use the TEN system to investigate the effects of ethanol, nutrition and ethanol/nutritional interactions on ethanol metabolism and clearance in pregnant and virgin rats and to identify the nutritional; endocrine; biochemical and molecular mechanisms underlying these effects.