Ethanol and liver: Recent insights into the mechanisms of ethanol-induced fatty liver
Ethanol and liver: Recent insights into the mechanisms of ethanol-induced fatty liver
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DOI：
10.3748/wjg.v20.i40.14672
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发表时间：
2014-10-28
影响因子：
4.3
通讯作者：
Liu, Jinyao
中科院分区：
文献类型：
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作者：
Liu, Jinyao
酒精性脂肪性肝病(AFLD)是一种潜在的病理状态，可发展为脂肪性肝炎、纤维化和肝硬变，导致肝功能衰竭和死亡的可能性增加。酒精通过增加肝细胞中还原形式的烟酰胺腺嘌呤二核苷酸与氧化形式的烟酰胺腺嘌呤二核苷酸的比例，增加肝脏类固醇调节元件结合蛋白(SREBP)-1，纤溶酶原激活物抑制物(PAI)-1的活性和早期生长反应-1的活性，以及降低肝脏过氧化物酶体增殖物激活的受体-α的活性来诱导脂肪肝。酒精激活天然免疫系统，导致免疫反应失衡，随后激活的库普弗细胞衍生的肿瘤坏死因子-α过度产生，进而导致肝脏SREBP-1和PAI-1活性的变化。酒精滥用促进骨髓源性细胞(BMDCs)向肝脏的迁移，然后重新编程BMDCs的肿瘤坏死因子-α的表达。慢性酒精摄入会触发交感神经过度活跃激活的肝星状细胞(HSC)反馈环，进而激活HSC，导致HSC衍生的肿瘤坏死因子-α产生过量。卡维地洛可能通过抑制交感神经活动来阻断这一反馈回路，从而延缓AFLD的进展。评估卡维地洛与肿瘤坏死因子-α抑制剂联合治疗AFLD患者的临床研究有必要防止酒精性肝病的发展。(C)2014百仕登出版集团有限公司，版权所有。
Alcoholic fatty liver disease (AFLD), a potentially pathologic condition, can progress to steatohepatitis, fibrosis, and cirrhosis, leading to an increased probability of hepatic failure and death. Alcohol induces fatty liver by increasing the ratio of reduced form of nicotinamide adenine dinucleotide to oxidized form of nicotinamide adenine dinucleotide in hepatocytes; increasing hepatic sterol regulatory element-binding protein (SREBP)-1, plasminogen activator inhibitor (PAI)-1, and early growth response-1 activity; and decreasing hepatic peroxisome proliferator-activated receptor-alpha activity. Alcohol activates the innate immune system and induces an imbalance of the immune response, which is followed by activated Kupffer cell-derived tumor necrosis factor (TNF)-alpha overproduction, which is in turn responsible for the changes in the hepatic SREBP-1 and PAI-1 activity. Alcohol abuse promotes the migration of bone marrow-derived cells (BMDCs) to the liver and then reprograms TNF-alpha expression from BMDCs. Chronic alcohol intake triggers the sympathetic hyperactivity-activated hepatic stellate cell (HSC) feedback loop that in turn activates the HSCs, resulting in HSC-derived TNF-alpha overproduction. Carvedilol may block this feedback loop by suppressing sympathetic activity, which attenuates the progression of AFLD. Clinical studies evaluating combination therapy of carvedilol with a TNF-alpha inhibitor to treat patients with AFLD are warranted to prevent the development of alcoholic liver disease. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.