Horie Y, Ishii H
Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Nihon Arukoru Yakubutsu Igakkai Zasshi. 2001 Oct;36(5):471-85.
Although alcohol is well recognized as a systemic toxin, the enteric manifestations of alcohol abuse have only recently begun to be elucidated at the cellular and microvascular levels. Since the microvascular mechanism of the toxicity of alcohol has progressively been revealed, clinical applications of this research field should increase the availability of therapeutic options for alcohol-induced injuries of liver, pancreas and gastrointestinal (GI) tract. A high concentration of ethanol reduces GI and pancreas blood flow. Ethanol-induced GI hemorrhage, GI ulcer, and pancreatitis are initiated by the microcirculatory disturbance of GI mucosa and pancreas. Ethanol administration induces an increase in vasoactive agents such as endothelin and nitric oxide and oxidative stress. They appear to be involved in ethanol-induced GI and pancreatic injury. Regarding the effects of ethanol on the liver, small amount of ethanol increases hepatic blood flow, and prevents gut ischemia/reperfusion (I/R)-induced hepatic microvascular dysfunction and subsequent liver injury. While large amount of ethanol itself causes hepatic microvascular dysfunction, and aggravates the gut I/R-induced hepatic microvascular dysfunction and subsequent liver injury. Vasoactive agents and oxidative stress also appear to be involved in the liver injury. In endotoxemic animals, even small amount of ethanol causes hepatic microvascular dysfunction. Chronic ethanol consumption aggravates endotoxin-induced hepatic microvascular dysfunction. Chronic ethanol consumption aggravates gut I/R-induced leukostasis in the liver and hepatocellular injury associated with an enhanced expression of adhesion molecules, while it prevents the gut I/R-induced sinusoidal perfusion injury. Thus, effects of chronic ethanol consumption on the I/R injury are still controversial.
尽管酒精被公认为是一种全身性毒素，但酒精滥用的肠道表现直到最近才开始在细胞和微血管水平上得到阐明。随着酒精毒性的微血管机制逐渐被揭示，该研究领域的临床应用应会增加针对酒精所致肝、胰腺和胃肠道损伤的治疗选择。高浓度乙醇会减少胃肠道和胰腺的血流量。乙醇诱导的胃肠道出血、胃溃疡和胰腺炎是由胃肠道黏膜和胰腺的微循环紊乱引发的。给予乙醇会导致血管活性物质如内皮素和一氧化氮增加以及氧化应激。它们似乎参与了乙醇诱导的胃肠道和胰腺损伤。关于乙醇对肝脏的影响，少量乙醇会增加肝血流量，并预防肠道缺血/再灌注（I/R）诱导的肝微血管功能障碍及随后的肝损伤。而大量乙醇本身会导致肝微血管功能障碍，并加重肠道I/R诱导的肝微血管功能障碍及随后的肝损伤。血管活性物质和氧化应激似乎也参与了肝损伤。在内毒素血症动物中，即使少量乙醇也会导致肝微血管功能障碍。长期饮酒会加重内毒素诱导的肝微血管功能障碍。长期饮酒会加重肠道I/R诱导的肝脏白细胞淤滞以及与黏附分子表达增强相关的肝细胞损伤，而它会预防肠道I/R诱导的肝血窦灌注损伤。因此，长期饮酒对I/R损伤的影响仍存在争议。
