ETHANOL METABOLISM IN PREGNANCY--ROLE OF DIET

描述(摘自申请人的摘要)：众所周知， 女性比男性更容易受到酒精不良影响的影响。一个 据估计，5%-20%的美国女性在怀孕期间饮酒。然而， 几乎没有研究考察乙醇对怀孕母亲的影响。 我们开发了一种全肠内营养(TEN)模型，支持 妊娠的额外营养需求，这使得系统性的 这一时期的乙醇代谢和处置的研究。使用这十个 我们已经做了几个重要的观察：第一，不变的 输注乙醇，男性和男性血液和尿液乙醇浓度 未怀孕的雌性大鼠的周期在几乎为零到超过500 mg/dl之间， 每6天一个脉冲的频率。这就是看起来像是 是乙醇依赖增加所介导的“循环”乙醇代谢。 肝脏主要乙醇代谢酶，ADH类。第二，地震的幅度 这些乙醇脉冲在怀孕的雌性大鼠中显著减少(65%) 与处女大鼠相比，注入相同水平的乙醇和卡路里 这表明怀孕期间乙醇代谢显著增加。 这将是保护的，因为在给定的条件下，乙醇新陈代谢的速度 乙醇摄入量，决定母亲血液中乙醇浓度和 毒性。第三，我们观察到怀孕期间营养不良 将脉动乙醇浓度的幅度显著提高到 更高的水平。这预计会增加母体的毒性。我们 假设乙醇代谢和清除量显著增加 在营养良好的怀孕大鼠中，内分泌变化和 能量摄入增加导致肝脏ADH表达增加 此外，我们假设怀孕期间营养不良会导致 在ADH依赖的乙醇代谢受损，这将导致增加 乙醇对母亲和胎儿都有毒性。当前提案的目标 是使用TEN系统来研究酒精、营养和 乙醇/营养互作对乙醇代谢和清除的影响 并鉴定孕鼠和处女大鼠的营养；内分泌； 这些效应背后的生化和分子机制。

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.