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酒精性肝病中的异常血浆脂蛋白和卵磷脂胆固醇酰基转移酶缺乏

Abnormal plasma lipoproteins and lecithin-cholesterol acyltransferase deficiency in alcoholic liver disease.

作者信息

Sabesin S M, Hawkins H L, Kuiken L, Ragland J B

出版信息

Gastroenterology. 1977 Mar;72(3):510-8.

PMID:188710
Abstract

Serial studies of plasma lipids and lipoproteins were performed in 4 patients with acute alcoholic liver disease characterized by a massive fatty liver and laboratory evidence of intrahepatic cholestasis. There were striking alterations in the plasma lipoprotein electrophoretic patterns characterized by the absence of alpha- and pre-beta-lipoprotein bands and the presence of a single band of abnormal mobility. These changes were associated with an extreme decrease in plasma lecithin-cholesterol acyltransferase activity, resulting in greatly reduced levels of plasma cholesteryl esters and increased levels of unesterified cholesterol. In 2 patients hypertriglyceridemia and hypercholesterolemia were present, the latter because of an increase in unesterified cholesterol. Lipoproteins were isolated from the plasma by sequential ultracentrifugation at the densities used for separation of normal very low density, low density, and high density lipoproteins; however, the patients' lipoproteins were different from normal in lipid composition and ultrastructure. All of the lipoprotein fractions were decreased in cholesteryl esters and the major lipoprotein was a triglyceride-rich low density lipoprotein. Electron microscopic studies of the low and high density lipoprotein fractions revealed the presence of bilamellar vesicles and stacked discs. All of the changes in lipoprotein composition and ultrastructure gradually returned to normal with clinical improvement. These observations indicate that alcoholic liver injury is associated with profound alterations in lipoprotein composition and metabolism which may be related in part to lecithin-cholesterol acyltransferase deficiency.

摘要

对4例以大量脂肪肝和肝内胆汁淤积实验室证据为特征的急性酒精性肝病患者进行了血浆脂质和脂蛋白的系列研究。血浆脂蛋白电泳图谱有显著改变,其特征是缺乏α-脂蛋白和前β-脂蛋白条带,出现一条迁移率异常的单一条带。这些变化与血浆卵磷脂胆固醇酰基转移酶活性极度降低有关,导致血浆胆固醇酯水平大幅降低,未酯化胆固醇水平升高。2例患者出现高甘油三酯血症和高胆固醇血症,后者是由于未酯化胆固醇增加所致。通过在用于分离正常极低密度脂蛋白、低密度脂蛋白和高密度脂蛋白的密度下进行连续超速离心从血浆中分离脂蛋白;然而,患者的脂蛋白在脂质组成和超微结构上与正常脂蛋白不同。所有脂蛋白组分的胆固醇酯均减少,主要脂蛋白是富含甘油三酯的低密度脂蛋白。对低密度和高密度脂蛋白组分的电子显微镜研究显示存在双分子层囊泡和堆叠圆盘。随着临床改善,脂蛋白组成和超微结构的所有变化逐渐恢复正常。这些观察结果表明,酒精性肝损伤与脂蛋白组成和代谢的深刻改变有关,这可能部分与卵磷脂胆固醇酰基转移酶缺乏有关。

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