Department of Pathobiology, Cleveland Clinic, Cleveland, Ohio 44195, USA.
J Dig Dis. 2011 Feb;12(1):3-9. doi: 10.1111/j.1751-2980.2010.00468.x.
The development of alcoholic liver disease (ALD) is a complex process involving both the parenchymal and non-parenchymal cells in the liver. The impact of ethanol on hepatocytes can be characterized as a condition of organelle stress with multifactorial changes in hepatocellular function accumulating during ethanol exposure. These changes include oxidative stress, mitochondrial dysfunction, decreased methylation capacity, endoplasmic reticulum stress, impaired vesicular trafficking and altered proteasome function. Injury to hepatocytes is attributed, in part, to ethanol metabolism by the hepatocytes. Changes in the structural integrity of hepatic sinusoidal endothelial cells, as well as enhanced inflammation in the liver during ethanol exposure are also important contributors to injury. Activation of hepatic stellate cells initiates the deposition of extracellular matrix proteins characteristic of fibrosis. Kupffer cells, the resident macrophages in the liver, are particularly critical to the onset of ethanol-induced liver injury. Chronic ethanol exposure sensitizes Kupffer cells to activation by lipopolysaccharides via toll-like receptor 4. This sensitization enhances the production of inflammatory mediators, such as tumor necrosis factor-α and reactive oxygen species that contribute to hepatocyte dysfunction, necrosis and apoptosis of hepatocytes and the generation of extracellular matrix proteins leading to fibrosis. In this review we provide an overview of the complex interactions between parenchymal and non-parenchymal cells in the liver during the progression of ethanol-induced liver injury.
酒精性肝病（ALD）的发展是一个涉及肝脏实质细胞和非实质细胞的复杂过程。乙醇对肝细胞的影响可被描述为细胞器应激的状态，在乙醇暴露期间，肝细胞功能的多种因素变化逐渐积累。这些变化包括氧化应激、线粒体功能障碍、甲基化能力下降、内质网应激、囊泡运输受损以及蛋白酶体功能改变。肝细胞损伤部分归因于肝细胞对乙醇的代谢。在乙醇暴露期间，肝窦内皮细胞的结构完整性改变以及肝脏炎症的增强也是损伤的重要原因。肝星状细胞的激活启动了纤维化特征性的细胞外基质蛋白的沉积。库普弗细胞是肝脏中的常驻巨噬细胞，对乙醇诱导的肝损伤的发生尤为关键。慢性乙醇暴露通过 Toll 样受体 4 使库普弗细胞对脂多糖的激活敏感。这种敏化作用增强了炎症介质的产生，如肿瘤坏死因子-α和活性氧，导致肝细胞功能障碍、坏死和凋亡，以及细胞外基质蛋白的产生，导致纤维化。在这篇综述中，我们概述了在乙醇诱导的肝损伤进展过程中，肝脏实质细胞和非实质细胞之间的复杂相互作用。
