论文部分内容阅读
酒精性肝病(ALD)的发生是一个肝实质细胞与非实质细胞共同参与的复杂过程。乙醇对肝细胞的影响以细胞器应激为特征,肝细胞功能发生多种改变,并在乙醇暴露期间逐渐累积。这些改变包括氧化应激、线粒体功能障碍、甲基化能力降低、内质网应激、囊泡转运受损和蛋白酶体功能改变。肝细胞损伤部分归因于肝细胞对乙醇的代谢。乙醇暴露时肝窦内皮细胞结构完整性的改变和肝内炎症反应增强亦为肝损伤的重要成因。肝纤维化以肝星状细胞活化引起的细胞外基质蛋白沉积为特征。肝脏驻留型巨噬细胞Kupffer细胞对乙醇诱导肝损伤的发生尤为关键。长期乙醇暴露使Kupffer细胞对脂多糖通过Toll样受体4产生的激活作用敏感性增强。这一致敏作用使炎症介质如肿瘤坏死因子-α(TNF-α)和活性氧簇(ROS)产生增加,导致肝细胞功能异常、坏死凋亡以及细胞外基质蛋白产生,引起肝纤维化。本文对乙醇诱导肝损伤的进展过程中,肝实质细胞与非实质细胞间复杂的相互作用作一概述。
Occurrence of alcoholic liver disease (ALD) is a complicated process in which hepatic parenchymal cells and non-parenchymal cells participate together. The effect of ethanol on hepatocytes is characterized by organelle stress, with many changes in hepatocyte function and gradual accumulation during ethanol exposure. These changes include oxidative stress, mitochondrial dysfunction, decreased methylation, endoplasmic reticulum stress, impaired vesicular transport and altered proteasome function. Liver cell damage is due in part to hepatocyte metabolism of ethanol. Changes in the structural integrity of sinusoid endothelial cells during ethanol exposure and an increased intrahepatic inflammatory response are also important causes of liver injury. Liver fibrosis is characterized by deposition of extracellular matrix proteins caused by hepatic stellate cell activation. Liver-resident macrophage Kupffer cells are particularly critical for ethanol-induced liver injury. Prolonged ethanol exposure sensitizes Kupffer cells to the activation of lipopolysaccharide by Toll-like receptor 4. This sensitization increases the production of inflammatory mediators such as tumor necrosis factor-α (TNF-α) and reactive oxygen species (ROS), resulting in dysfunction of hepatocytes, necrosis and extracellular matrix protein production and hepatic fibrosis. This article summarizes the complex interactions between hepatic parenchymal cells and non-parenchymal cells during the progression of ethanol-induced liver injury.