Department of Pathology, The University of Texas Medical Branch, Galveston, TX 77555, USA.
Toxicol Appl Pharmacol. 2011 Sep 1;255(2):127-37. doi: 10.1016/j.taap.2011.05.022. Epub 2011 Jun 26.
Alcoholic liver disease (ALD) is a serious health problem with significant morbidity and mortality. In this study we examined the progression of ALD along with lipidomic changes in rats fed ethanol for 2 and 3 months to understand the mechanism, and identify possible biomarkers. Male Fischer 344 rats were fed 5% ethanol or caloric equivalent of maltose-dextrin in a Lieber-DeCarli diet. Animals were killed at the end of 2 and 3 months and plasma and livers were collected. Portions of the liver were fixed for histological and immunohistological studies. Plasma and the liver lipids were extracted and analyzed by nuclear magnetic resonance (NMR) spectroscopy. A time dependent fatty infiltration was observed in the livers of ethanol-fed rats. Mild inflammation and oxidative stress were observed in some ethanol-fed rats at 3 months. The multivariate and principal component analysis of proton and phosphorus NMR spectroscopy data of extracted lipids from the plasma and livers showed segregation of ethanol-fed groups from the pair-fed controls. Significant hepatic lipids that were increased by ethanol exposure included fatty acids and triglycerides, whereas phosphatidylcholine (PC) decreased. However, both free fatty acids and PC decreased in the plasma. In liver lipids unsaturation of fatty acyl chains increased, contrary to plasma, where it decreased. Our studies confirm that over-accumulation of lipids in ethanol-induced liver steatosis accompanied by mild inflammation on long duration of ethanol exposure. Identified metabolic profile using NMR lipidomics could be further explored to establish biomarker signatures representing the etiopathogenesis, progression and/or severity of ALD.
酒精性肝病（ALD）是一种严重的健康问题，具有显著的发病率和死亡率。在这项研究中，我们研究了大鼠在摄入乙醇 2 个月和 3 个月期间的 ALD 进展和脂质组学变化，以了解其机制，并确定可能的生物标志物。雄性 Fischer 344 大鼠喂食 5%乙醇或麦芽糊精的等热量麦芽糖。在 Lieber-DeCarli 饮食中。在 2 个月和 3 个月结束时处死动物，并收集血浆和肝脏。部分肝脏用于组织学和免疫组织化学研究。提取血浆和肝脏脂质并用核磁共振（NMR）光谱法分析。在乙醇喂养的大鼠肝脏中观察到时间依赖性脂肪浸润。在 3 个月时，一些乙醇喂养的大鼠观察到轻度炎症和氧化应激。来自血浆和肝脏的提取脂质的质子和磷 NMR 光谱数据的多元和主成分分析显示，乙醇喂养组与配对喂养对照组分离。乙醇暴露导致肝脂质增加的显著脂肪酸和甘油三酯增加，而磷脂酰胆碱（PC）减少。然而，游离脂肪酸和 PC 在血浆中均减少。在肝脏脂质中，脂肪酸链的不饱和性增加，与血浆相反，其不饱和性降低。我们的研究证实，在长期乙醇暴露下，乙醇诱导的肝脂肪变性中脂质过度积累伴随着轻度炎症。使用 NMR 脂质组学鉴定的代谢特征可进一步探索，以建立代表 ALD 的发病机制、进展和/或严重程度的生物标志物特征。
