Gentry-Nielsen Martha J, Top Elizabeth Vander, Snitily Mary U, Casey Carol A, Preheim Laurel C
Creighton University, and the Veterans Affairs Medical Center, Omaha, NE 68105, USA.
Alcohol Clin Exp Res. 2004 Jul;28(7):1120-8. doi: 10.1097/01.alc.0000136383.45378.91.
Although scientists have used animal models for years to study the effects of ethanol (EtOH) ingestion on humans, the compounding effect of cigarette smoking has been virtually ignored. Because 80 to 95% of human alcoholics smoke, it is imperative to consider the added effects of smoking when trying to determine the consequences of excessive alcohol ingestion. We therefore have developed a rat model for studying the separate and combined results of smoking and drinking on human health.
Male Sprague-Dawley rats were exposed daily for 12 weeks in whole-body chambers to cigarette smoke (smoke-exposed) or room air (sham-exposed). During the final 5 weeks of exposure, the rats were fed liquid diets that contained 0, 16, 26, or 36% EtOH calories. Smoke exposure was quantified by measurement of carboxyhemoglobin, nicotine, and cotinine levels. Body weights, food consumption, blood EtOH concentrations, and various assessments of liver damage and function also were followed.
Smoke exposure in this rat model approximates that of a moderate to heavy human smoker. Smoke-exposed rats weighed significantly less and ate less food than sham-exposed controls, but both groups ingested equivalent amounts of EtOH for their body weights and had comparable blood EtOH levels. Liver aspartate and alanine aminotransferase levels remained normal. There was an EtOH-induced decrease in asialoglycoprotein receptor binding, but it was not exacerbated by smoke exposure. Alterations in blood cholesterol levels reflected what has been reported for humans, rising with increasing EtOH ingestion and decreasing with smoke exposure.
Our rat model is relevant to what transpires in the vast majority of alcoholics. Both ethanol ingestion and smoke exposure can be manipulated to mimic light to moderate to heavy levels, making it appropriate for studying the separate and combined biomedical consequences of alcohol abuse and cigarette smoking.
尽管科学家多年来一直使用动物模型来研究乙醇(EtOH)摄入对人类的影响,但吸烟的复合效应实际上一直被忽视。由于80%至95%的人类酗酒者吸烟,在试图确定过量饮酒的后果时,必须考虑吸烟的附加影响。因此,我们开发了一种大鼠模型,用于研究吸烟和饮酒对人类健康的单独及联合影响。
将雄性Sprague-Dawley大鼠每天在全身舱中暴露于香烟烟雾(烟雾暴露组)或室内空气(假暴露组)中,持续12周。在暴露的最后5周,给大鼠喂食含有0%、16%、26%或36%乙醇热量的液体饮食。通过测量碳氧血红蛋白、尼古丁和可替宁水平来量化烟雾暴露情况。还跟踪了体重、食物摄入量、血液乙醇浓度以及对肝脏损伤和功能的各种评估。
该大鼠模型中的烟雾暴露情况接近中度至重度人类吸烟者。与假暴露对照组相比,烟雾暴露组大鼠体重明显更轻,食物摄入量更少,但两组按体重摄入的乙醇量相当,血液乙醇水平也相当。肝脏天冬氨酸和丙氨酸转氨酶水平保持正常。乙醇导致去唾液酸糖蛋白受体结合减少,但烟雾暴露并未使其加剧。血液胆固醇水平的变化反映了人类的相关报道,随着乙醇摄入量增加而升高,随着烟雾暴露而降低。
我们的大鼠模型与绝大多数酗酒者的情况相关。乙醇摄入和烟雾暴露均可进行调控,以模拟轻度至中度至重度水平,这使其适合用于研究酒精滥用和吸烟的单独及联合生物医学后果。