Department of Medicine, Rush University, Chicago, IL, USA.
Alcohol. 2010 Aug;44(5):447-56. doi: 10.1016/j.alcohol.2010.05.004. Epub 2010 Jul 3.
Alcohol and nonsteroidal anti-inflammatory drugs are noxious agents that can disrupt the integrity of the gastroduodenal mucosal and damage the epithelial barrier and lead to increased gastroduodenal permeability. Moreover, it is not uncommon that patients are exposed to these two barrier stressors at the same time. It is thus important to know how simultaneous exposure affects the gastroduodenal barrier, and acquiring that knowledge was the goal of this study. We used a method that has been widely used for the assessment of injury to the gastroduodenal barrier induced by these noxious agents-measurement of gastroduodenal permeability as indicated by urinary excretion of ingested sucrose. We used gas chromatography to measure the amount of sucrose excreted in the urine over the 5-12h after ingestion of a bolus of sucrose. The 148 participants in the study included 92 alcoholics and 56 healthy controls. All study subjects had a baseline permeability test. To determine whether addition of a second noxious agent, in addition to chronic alcohol, further decreases gastroduodenal barrier integrity, a subset of 118 study subjects participated in another permeability test in which they were exposed to aspirin. For this test, participants ingested 1,300 mg aspirin twice, 12 and 1h before the final permeability test. The baseline permeability test showed that alcoholics have significantly higher gastroduodenal permeability than controls. Aspirin caused a significant within-group absolute increase in gastroduodenal permeability in both alcoholics and controls (+7.72%, P=.003 and +2.25%, P=.011, respectively), but the magnitude of these increases was not significantly different from each other. Baseline permeability did vary by gender, self-reported illegal drug use, and employment type. The extent of the permeability increase after aspirin ingestion varied with illegal drug use and recruitment site (a surrogate marker of socioeconomic status). Our data show that alcoholics have greater gastroduodenal permeability than healthy controls. This difference was independent of the duration of any preceding period of sobriety, gender, smoking history, or illicit drug abuse. The injurious effects of alcohol on the gastroduodenal epithelial barrier are long lasting, persisting even after 7 days of sobriety. Although, acute aspirin and chronic alcohol each increase intestinal permeability in alcoholics, their effects appear to be additive rather than synergistic.
酒精和非甾体抗炎药是有害的物质，它们会破坏胃十二指肠黏膜的完整性，损害上皮屏障，导致胃十二指肠通透性增加。此外，患者同时接触这两种屏障应激源的情况并不少见。因此，了解同时暴露对胃十二指肠屏障的影响非常重要，而获得这方面的知识是本研究的目标。我们使用了一种广泛用于评估这些有害物质引起的胃十二指肠屏障损伤的方法，即通过摄入蔗糖后尿液中蔗糖的排泄来测量胃十二指肠通透性。我们使用气相色谱法测量摄入蔗糖后 5-12 小时内尿液中蔗糖的排泄量。这项研究共有 148 名参与者，其中包括 92 名酗酒者和 56 名健康对照者。所有研究对象都进行了基线通透性测试。为了确定除慢性酒精外，添加第二种有害物是否会进一步降低胃十二指肠屏障的完整性，研究对象中有 118 人参加了另一项通透性测试，他们在测试中摄入了阿司匹林。对于这项测试，参与者在最后一次通透性测试前 12 小时和 1 小时，分两次摄入 1300 毫克阿司匹林。基线通透性测试显示，酗酒者的胃十二指肠通透性明显高于对照组。阿司匹林在酗酒者和对照组中都引起了胃十二指肠通透性的显著内组绝对增加（分别为+7.72%，P=.003 和+2.25%，P=.011），但这种增加的幅度彼此之间没有显著差异。基线通透性确实因性别、自我报告的非法药物使用和就业类型而有所不同。摄入阿司匹林后通透性增加的程度因非法药物使用和招募地点（社会经济地位的替代标志物）而异。我们的数据显示，酗酒者的胃十二指肠通透性高于健康对照组。这种差异独立于任何先前戒酒期的持续时间、性别、吸烟史或非法药物滥用。酒精对胃十二指肠上皮屏障的损伤作用是持久的，即使在戒酒 7 天后仍持续存在。虽然急性阿司匹林和慢性酒精都会增加酗酒者的肠道通透性，但它们的作用似乎是相加的，而不是协同的。
