Ｍａｌｌｏｒｙ ｂｏｄｙ（アルコールしょう子体）形成機序に関する研究 ＤＤＣ投与によるマウス肝の形態的変化を中心に

Abstract

Male mice were fed a diet containing various concentrations of 3, 5-diethoxycarbonly-1, 4-dihyd-rocollidine (DDC) for 20 to 95 days. The livers of the mice were examined by light, electron and fluorescent microscopy. The following results were obtained :1) Mice fed daily a diet containing more than 0.1% DDC developed Mallory bodies (MBs) after 40 days regardless of the DDC concentration in the diet. After 60 days, MBs were more numerous in the mice fed higher concentrations of DDC. Some of the mice fed 0.05% DDC for 40 to 60 days developed MBs following an additional treatment of 2.5% DDC for 3 days. These results suggest that the formation of MBs in this animal model may involve two successive processes of cellular alteration which are termed priming and induction. Priming is the initial state which is time-dependent, whereas induction is the second stage which appears to be dose-dependent. During the priming stage marked hepatomegaly was observed and by light microscopy pale swollen hepatocytes were noted. In this stage the electron microscopic and immunofluorescent studies revealed that intermediate filaments (IFs) were increased in the hepatocytes. In the induction stage hepatomegaly was not as marked as that in the priming stage. At this stage MBs were observed in grossly misshapen hepatocytes. By immunofluorescent microscopy, MBs strongly reacted with anti-prekeratin antibody. However, the cytoplasmic stains of MB-containing hepatocytes were markedly decreased or totally absent. These observations suggest that the induction of MBs is caused by the aggregation of IFs, which are increased during the priming stage.2) MBs in the livers of mice fed DDC completely disappeared after the withdrawal of DDC from the diet for about 10 weeks. MBs reappeared in this group of mice following rechallenge of a higher concentration of DDC for one week.3) These events in the animal model might be analogus to the development of alcoholic hepatitis in patients with a history of heavey drinking for many years (priming) whose admission to the hospital was immediately preceded by a binge drinking (induction).4) It is probable that cytoskeletal changes similar to those observed in this animal model also occur in patients with alcoholic hepatitis and that those changes may constitute a major pathogenic factor of cell injury and necrosis in alcoholic liver disease.