Nanji A A, Yang E K, Fogt F, Sadrzadeh S M, Dannenberg A J
Department of Pathology, New England Deaconess Hospital, Boston, Massachusetts, USA.
J Pharmacol Exp Ther. 1996 Jun;277(3):1694-700.
Lipid peroxidation may be important in the pathogenesis of alcoholic liver injury. We investigated the potential of medium chain triglycerides and vitamin E to decrease lipid peroxidation and reverse established alcoholic liver injury. Four groups (five rats/group) of male Wistar rats were studied. Rats in group 1 were fed a fish oil-ethanol diet for 6 weeks. Rats in groups 2, 3 and 4 were fed the fish oil-ethanol diet for 6 weeks before being switched to fish oil-dextrose (group 2), fish oil-dextrose plus vitamin E (group 3) or medium chain triglycerides-dextrose (group 4) diets for 2 weeks. Liver samples were analyzed for histopathology, lipid peroxidation, fatty acid composition and cytochrome P450 2E1 activity. By 6 weeks, all rats developed fatty liver, inflammation and necrosis. After switching to the dextrose-containing diets, there was minimal histologic improvement in group 2, moderate improvement in group 3 and near normalization of the histology in group 4. Histologic improvement was associated with decreased lipid peroxidation and cytochrome P450 2E1 activity. Higher levels of polyunsaturated fatty acids were seen in groups 2 and 3 than in group 4. Our results indicate that a diet enriched in saturated (group 4) but not polyunsaturated (group 2) fatty acids effectively reverses alcoholic liver injury. Treatment with vitamin E also led to histologic improvement. These effects may be explained, at least in part, by down-regulation of lipid peroxidation. Other effects of medium chain triglycerides, such as their propensity for oxidation rather than esterification, may also be important.
脂质过氧化可能在酒精性肝损伤的发病机制中起重要作用。我们研究了中链甘油三酯和维生素E降低脂质过氧化及逆转已形成的酒精性肝损伤的潜力。对四组(每组五只大鼠)雄性Wistar大鼠进行了研究。第1组大鼠喂食鱼油 - 乙醇饮食6周。第2、3和4组大鼠先喂食鱼油 - 乙醇饮食6周,然后分别改为喂食鱼油 - 葡萄糖(第2组)、鱼油 - 葡萄糖加维生素E(第3组)或中链甘油三酯 - 葡萄糖(第4组)饮食2周。对肝脏样本进行组织病理学、脂质过氧化、脂肪酸组成和细胞色素P450 2E1活性分析。到6周时,所有大鼠均出现脂肪肝、炎症和坏死。改为含葡萄糖饮食后,第2组组织学改善极小,第3组有中度改善,第4组组织学接近正常。组织学改善与脂质过氧化和细胞色素P450 2E1活性降低有关。第2组和第3组的多不饱和脂肪酸水平高于第4组。我们的结果表明,富含饱和脂肪酸(第4组)而非多不饱和脂肪酸(第2组)的饮食可有效逆转酒精性肝损伤。维生素E治疗也导致组织学改善。这些作用至少部分可通过脂质过氧化的下调来解释。中链甘油三酯的其他作用,如它们易于氧化而非酯化的特性,可能也很重要。