PULSATILE BLOOD-ALCOHOL AND CYP2E1 INDUCTION DURING CHRONIC ALCOHOL INFUSIONS IN RATS
PULSATILE BLOOD-ALCOHOL AND CYP2E1 INDUCTION DURING CHRONIC ALCOHOL INFUSIONS IN RATS
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DOI：
10.1016/0741-8329(93)90064-u
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发表时间：
1993-11-01
期刊：
影响因子：
2.3
通讯作者：
HAKKAK, R
中科院分区：
文献类型：
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作者：
BADGER, TM;RONIS, MJJ;HAKKAK, R
成年雄性Sprague-Dawley大鼠使用全肠内营养模型用酒精处理35天。将胃内插管插入大鼠体内，并向大鼠输注旨在促进雄性大鼠正常生长的饲料。以总热量的35%注入酒精35天。测定尿液和血液中的酒精浓度，发现在连续酒精输注过程中是脉动的，其值在接近零和大于500 mg/dl之间。24小时尿酒精浓度被认为是血液酒精浓度（BAC）的良好指标。以两步方式诱导细胞色素P450 CYP 2 E1。第一步发生在BAC低于250 mg/dl时，其特征是活性和载脂蛋白水平显著升高（p <0.05），稳态mRNA无变化。第二步发生在BAC大于300 mg/dl的情况下，导致稳态mRNA水平显著升高（p小于或等于0.05）。我们提出，脉动BAC是由乙醇浓度依赖性调节乙醇代谢系统，可能CYP 2 E1。
Adult male Sprague-Dawley rats were treated with alcohol for 35 days using a total enteral nutrition model. Intragastric cannulae were inserted into rats and they were infused with a diet designed to promote normal growth in male rats. Alcohol was infused at 35% of total calories for 35 days. Urine and blood alcohol concentrations were determined and found to be pulsatile during continuous alcohol infusion, having values between near zero and greater than 500 mg/dl. Twenty-four-hour urine alcohol concentrations were found to be excellent indicators of blood alcohol concentrations (BACs). Cytochrome P450 CYP2E1 was induced in a two-step manner. Step one occurred at BACs below 250 mg/dl and was characterized by significant (p less than or equal to 0.05) elevations in activities and apoprotein levels with no changes in steady-state mRNA. Step two occurred with BACs greater than 300 mg/dl and resulted in significant (p less than or equal to 0.05) elevations in steady-state mRNA levels. We propose that the pulsatile BACs are caused by an ethanol concentration-dependent regulation of an ethanol metabolizing system, perhaps CYP2E1.