Ultrastructural and Immunohistochemical Study of Hepatic Fibrosis after the Ligation of the Common Bile Duct in Rats

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 α-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 α-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. (J Korean Pediatr Gastroenterol Nutr 1999; 2: 185∼193) ꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏ

[1]  N. Davidson,et al.  Retinoic acid and transforming growth factor beta differentially inhibit platelet-derived-growth-factor-induced Ito-cell activation. , 1991, The Biochemical journal.

[2]  M. Rissel,et al.  Reversibility of hepatic fibrosis in experimentally induced cholestasis in rat. , 1990, The American journal of pathology.

[3]  N. Davidson,et al.  Retinoic acid modulates rat Ito cell proliferation, collagen, and transforming growth factor beta production. , 1990, The Journal of clinical investigation.

[4]  N. Tavoloni,et al.  Origin, pattern, and mechanism of bile duct proliferation following biliary obstruction in the rat. , 1990, Gastroenterology.

[5]  M. Eghbali,et al.  Ito‐cell gene expression and collagen regulation , 1990, Hepatology.

[6]  F. Bianchi,et al.  Desmin and actin in the identification of Ito cells and in monitoring their evolution to myofibroblasts in experimental liver fibrosis , 1988, Virchows Archiv. B, Cell pathology including molecular pathology.

[7]  B. Davis,et al.  Retinol and extracellular collagen matrices modulate hepatic Ito cell collagen phenotype and cellular retinol binding protein levels. , 1987, The Journal of biological chemistry.

[8]  Y. Nakanuma,et al.  Immunohistochemical study on bile ductular proliferation in various hepatobiliary diseases. , 2008, Liver.

[9]  H. Popper General Pathology of the Liver: Light Microscopic Aspects Serving Diagnosis and Interpretation1 , 1986, Seminars in liver disease.

[10]  J. Haot,et al.  Cholestatic features in focal nodular hyperplasia of the liver. , 2008, Liver.

[11]  Y. Hasumura,et al.  The Role of Fat‐Storing Cells in Disse Space Fibrogenesis in Alcoholic Liver Disease , 2007, Hepatology.

[12]  T. Okanoue,et al.  The role of the Ito cell in perivenular and intralobular fibrosis in alcoholic hepatitis. , 1983, Archives of pathology & laboratory medicine.

[13]  R. Peters,et al.  The nature and origin of proliferated bile ductules in alcoholic liver disease. , 1983, American journal of clinical pathology.

[14]  R. Perez-Tamayo Cirrhosis of the liver: a reversible disease? , 1979, Pathology annual.

[15]  N. Buyssens Ductular proliferation. , 1965, Gastroenterology.

[16]  H. Popper,et al.  Has proliferation of bile ductules clinical significance? , 1962, Acta hepato-splenologica.

[17]  G. Millonig FURTHER OBSERVATIONS ON A PHOSPHATE BUFFER FOR OSMIUM SOLUTIONS IN FIXATION , 1962 .