Qin Xiaofa, Deitch Edwin A
Department of Surgery, Rutgers-New Jersey Medical School, Newark, NJ 07103, USA.
Department of Surgery, Rutgers-New Jersey Medical School, Newark, NJ 07103, USA.
Toxicol Lett. 2015 Jan 22;232(2):356-62. doi: 10.1016/j.toxlet.2014.11.027. Epub 2014 Nov 25.
Acute and/or chronic alcohol ingestion has been shown to exacerbate the morbidity and mortality rate associated with acute mechanical and/or thermal trauma. While alcohol ingestion can affect many organs and systems, clinical and preclinical studies indicate that alcohol ingestion can cause a 'leaky gut' syndrome which in turn contributes to infection and systemic organ dysfunction. This study investigated the acute effect of alcohol on gut barrier function. Using an in vivo isolated gut sac model of naïve male rats, each individual gut sac was injected with different concentrations (0, 5, 10, 20, and 40%, v/v) of alcohol. After different times of alcohol exposure, each isolated gut segment was harvested and intestinal permeability and mucosal surface hydrophobicity (a physiologic marker of mucus barrier function) were measured as well as luminal DNA, mucus, protein and free fatty acids. The results showed that alcohol caused dose-dependent and time-dependent increases in gut permeability and decreases in mucosal surface hydrophobicity, with significant changes to be observed 5 min after treatment with 10% alcohol. In addition, it is further found that these changes in permeability and hydrophobicity are more closely associated with increased intestinal luminal free fatty acids levels but not protein or DNA levels. These results suggest that alcohol may cause loss of gut barrier function by extracting and dissolving lipids from the mucus with a resultant decrease in mucosal surface hydrophobicity, which is a critical component of gut barrier function.
急性和/或慢性酒精摄入已被证明会加剧与急性机械性和/或热创伤相关的发病率和死亡率。虽然酒精摄入会影响许多器官和系统,但临床和临床前研究表明,酒精摄入会导致“肠漏”综合征,进而导致感染和全身器官功能障碍。本研究调查了酒精对肠道屏障功能的急性影响。使用未接触过酒精的雄性大鼠的体内离体肠囊模型,向每个单独的肠囊注射不同浓度(0、5、10、20和40%,v/v)的酒精。在酒精暴露不同时间后,收集每个离体肠段,测量肠道通透性和黏膜表面疏水性(黏液屏障功能的生理标志物)以及肠腔DNA、黏液、蛋白质和游离脂肪酸。结果表明,酒精导致肠道通透性呈剂量和时间依赖性增加,黏膜表面疏水性降低,在用10%酒精处理5分钟后可观察到显著变化。此外,进一步发现这些通透性和疏水性的变化与肠腔游离脂肪酸水平升高更密切相关,而与蛋白质或DNA水平无关。这些结果表明,酒精可能通过从黏液中提取和溶解脂质导致肠道屏障功能丧失,从而导致黏膜表面疏水性降低,而黏膜表面疏水性是肠道屏障功能的关键组成部分。