Massey Veronica L, Arteel Gavin E
Department of Pharmacology and Toxicology, University of Louisville Alcohol Research Center, University of Louisville Health Sciences Center Louisville, KY, USA.
Front Physiol. 2012 Jun 12;3:193. doi: 10.3389/fphys.2012.00193. eCollection 2012.
Alcohol consumption is customary in most cultures and alcohol abuse is common worldwide. For example, more than 50% of Americans consume alcohol, with an estimated 23.1% of Americans participating in heavy and/or binge drinking at least once a month. A safe and effective therapy for alcoholic liver disease (ALD) in humans is still elusive, despite significant advances in our understanding of how the disease is initiated and progresses. It is now clear that acute alcohol binges not only can be acutely toxic to the liver, but also can contribute to the chronicity of ALD. Potential mechanisms by which acute alcohol causes damage include steatosis, dysregulated immunity and inflammation, and altered gut permeability. Recent interest in modeling acute alcohol exposure has yielded new insights into potential mechanisms of acute injury, which also may well be relevant for chronic ALD. Recent work by this group on the role of PAI-1 and fibrin metabolism in mediating acute alcohol-induced liver damage serve as an example of possible new targets that may be useful for alcohol abuse, be it acute or chronic.
在大多数文化中,饮酒是一种习俗,而酗酒在全球范围内都很常见。例如,超过50%的美国人饮酒,估计有23.1%的美国人至少每月一次大量饮酒和/或暴饮。尽管我们对酒精性肝病(ALD)的发病和进展机制有了重大进展,但针对人类ALD的安全有效治疗方法仍然难以捉摸。现在很清楚,急性暴饮不仅会对肝脏产生急性毒性,还会导致ALD的慢性化。急性酒精造成损害的潜在机制包括脂肪变性、免疫失调和炎症以及肠道通透性改变。最近对模拟急性酒精暴露的研究为急性损伤的潜在机制带来了新的见解,这也很可能与慢性ALD相关。该团队最近关于纤溶酶原激活物抑制剂-1(PAI-1)和纤维蛋白代谢在介导急性酒精性肝损伤中的作用的研究,就是可能对酗酒(无论是急性还是慢性)有用的新靶点的一个例子。