사염화탄소 투여 쥐에서 아연이 간세포의 아포토시스와 TGF-ßl 분비에 미치는 영향

Abstract

Recently zinc has been known as a beneficial agent in the protection against hepatotoxicity and Its effect was supposed due to decreased hepatic cell apoptosis by the inhibition of endonuclease activity. Meanwhile, Transfonning growth factor-ß1 (TGF-ß1) was considered an important regulator in the pathogenesis of early hepatic fibrosis. The aim of this study was to ascertain the effect of zinc on hepatic cell apoptosis and TGF-ß1secretion in early hepatic fibrosis induced by carbon tetrachloride (CCl4). Twenty male Wistar rats were divided into four groups: the control group, control + zinc treated group, CCl4 treated group and CCl4+zinc treated group. All the rats were sacrified 8 days later for histological and biochemical assessments. The collagen content in liver wasmeasured after Masson’s trichrome staining, apoptosis was detected by terminal UDP-nick end labelling (TUNEL) staining and TGF-ß1 was quantified by labelled streptavidin biotin (LSAB) immunostaining using a computerized image analysis system. TUNEL-positive cells (apoptotic cel1s) increased in rats with early hepatic fibrosis and oral zinc administration decreased the number of apoptotic cells in the CCl4-treated rats. The zinc-mediated decrease of apoptosis in the liver was related to an increase of TGF-ßl positive cel1s and collagen content. However, AST, ALT levels and the number of fatty changed hepatic cel1s as an index of hepatic cell damage increased in rats with early hepatic fibrosis and two indices decreased by zinc administration. These results suggest that apoptosis may be involved, together with necrosis, in the early hepatic fibrogenesis and was closely related to the increase of TGF-ß1secretion and collagen content. Therefore, zinc could play an important role in the inhibition of early hepatic fibrosis induced by CCl4.