Moreira E, Fontana L, Periago J L, Sanchéz De Medina F, Gil A
Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad de Granada, Spain.
Hepatology. 1995 Jan;21(1):199-206.
The aim of this study was to evaluate the changes in fatty acid composition of lipids of plasma, erythrocytes, and liver microsomes in rats with liver cirrhosis induced by oral intake of thioacetamide and to determine to what extent the experimental model reproduces the fatty acid tissue alterations reported in human cirrhosis. Two groups of rats were studied. The control group received water ad libitum, and the experimental group received 0.03% w/v thioacetamide in drinking water for 2, 4, and 6 months. At these times, lipids of plasma, erythrocytes, and liver microsomes were extracted, and their fatty acid compositions were determined. Thioacetamide intake led to macronodular and micronodular cirrhosis at 2 months. These alterations progressed at 4 months and eventuated in liver tumors at 6 months. Thioacetamide-treated rats showed a drop in total plasma fatty acids, higher percentages of palmitic acid in all lipid fractions, and lower levels of stearic acid in erythrocyte lipids and liver microsomal phospholipids. Oleic acid increased in plasma cholesteryl esters and phospholipids, as well as in erythrocyte lipids and liver microsomal phospholipids. In plasma lipids and liver microsomal phospholipids, the percentages of arachidonic and docosahexaenoic acids decreased. The latter also decreased in erythrocyte lipids. In addition, liver microsomes showed a higher cholesterol/lipid phosphorus molar ratio. The experimental model of cirrhosis obtained by intake of thioacetamide in drinking water for 4 months reproduces many of the fatty acid tissue alterations that appear in human cirrhosis and may serve to ascertain the biochemical mechanisms involved in these changes.
本研究的目的是评估经口摄入硫代乙酰胺诱导肝硬化的大鼠血浆、红细胞和肝微粒体脂质中脂肪酸组成的变化，并确定该实验模型在多大程度上再现了人类肝硬化中报道的脂肪酸组织改变。研究了两组大鼠。对照组随意饮水，实验组饮用含0.03% w/v硫代乙酰胺的水2、4和6个月。在这些时间点，提取血浆、红细胞和肝微粒体的脂质，并测定其脂肪酸组成。摄入硫代乙酰胺在2个月时导致大结节性和小结节性肝硬化。这些改变在4个月时进展，并在6个月时最终发展为肝肿瘤。经硫代乙酰胺处理的大鼠血浆总脂肪酸下降，所有脂质组分中棕榈酸百分比升高，红细胞脂质和肝微粒体磷脂中硬脂酸水平降低。油酸在血浆胆固醇酯和磷脂、红细胞脂质和肝微粒体磷脂中增加。在血浆脂质和肝微粒体磷脂中，花生四烯酸和二十二碳六烯酸的百分比下降。后者在红细胞脂质中也下降。此外，肝微粒体显示出更高的胆固醇/脂质磷摩尔比。通过饮用含硫代乙酰胺的水4个月获得的肝硬化实验模型再现了人类肝硬化中出现的许多脂肪酸组织改变，并可能有助于确定这些变化所涉及的生化机制。
