ABSTRACT
PURPOSE: Proliferation of bile duct-like structures and fibrosis is a hepatic cellular reaction observed in most forms of human liver disease and in a variety of experimental conditions associated with liver injury. The aim of this study was to investigate the activation of Ito cells and bile duct proliferation in the rat after common bile duct ligation (CBDL). METHODS: Hepatic morphological abnormalities were examined in rats whose bile ducts had been irreversibly ligated for 15, 21, 24 and 28 days. The liver was examined by immunohistochemical staining for alpha-smooth muscle actin, the known marker of activated Ito cells, and light and electron microscopes. RESULTS: After CBDL, the bile canalicular proliferation and interstitial fibrosis were gradually increased in the periportal areas extended to hepatic sinusoids. Ito cells positive for alpha-smooth muscle actin were frequently observed in the periductular space and in perisinusoidal space of Disse. Ito cells and myofibroblasts were gradually increased in the interstitial fibrosis until the 28th day after CBDL. Ito cells and myofibroblasts had microfilaments with dense body at the periphery of the cell. CONCLUSIONS: Our results suggest that Ito cells may be fibroblastic or myogenic. It has also been postulated that during the development of hepatic fibrosis, Ito cells become myofibroblasts or fibroblast like cells.