title: Tissue remodeling following submassive hemorrhagic necrosis in rat livers induced by an intraperitoneal injection of dimethylnitrosamine.
abstract: We examined regeneration and fibrosis in the necrotic areas of hepatic stellate cells (HSCs). Acute hepatic injury was induced in rats by administration of an intraperitoneal injection of high-dose dimethylnitrosamine (50 mg/kg body weight). Liver samples were obtained from rats 6, 12, 24, 36 h and 2, 3, 5, 7, 10, and 14 days after the injection. They were examined by light and electron microscopy and by immunohistochemical methods. Hemorrhagic necrosis became most prominent 36 h after treatment and extended into zones 3 and 2. In the submassive necrotic areas the sinusoidal structure was destroyed. No HSCs positive for alpha-smooth muscle actin or desmin were present. On day 5, when necrotic tissues were almost removed by infiltrating macrophages, HSCs strongly positive for alpha-smooth muscle actin and desmin appeared along the surface of the preserved parenchyma and migrated into the necrotic areas along the residual reticulin fibers. By day 14 most of the necrotic areas were almost completely replaced by the regeneration of hepatocytes and central to central (C-C) bridging fibrosis. Our results indicate that following submassive complete necrosis, HSCs in the preserved liver parenchyma have roles in the formation of sinusoidal wall for remodeling in necrotic areas via their activation, proliferation, and migration into the necrotic areas.
authors.affiliation: First Department of Pathology, Kochi Medical School, Kohasu, Oko-cho, Nankoku City, Kochi, 783-8505, Japan. jyl@kochi-ms.ac.jp
authors.forename: Yu-Lan
authors.initials: YL
authors.lastname: Jin
authors.forename: Hideaki
authors.initials: H
authors.lastname: Enzan
authors.forename: Naoto
authors.initials: N
authors.lastname: Kuroda
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Nakayama
authors.forename: Yan-Hu
authors.initials: YH
authors.lastname: Zhang
authors.forename: Makoto
authors.initials: M
authors.lastname: Toi
authors.forename: Eriko
authors.initials: E
authors.lastname: Miyazaki
authors.forename: Makoto
authors.initials: M
authors.lastname: Hiroi
authors.forename: Li-Mei
authors.initials: LM
authors.lastname: Guo
authors.forename: Toshiji
authors.initials: T
authors.lastname: Saibara
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002455:Cell Division; D002465:Cell Movement; D003893:Desmin / Q000378:metabolism; D004128:Dimethylnitrosamine / Q000008:administration & dosage; D004195:Disease Models, Animal; D006470:Hemorrhage / Q000209:etiology / Q000473:pathology*; D007274:Injections, Intraperitoneal; D007728:Kupffer Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D008106:Liver Cirrhosis, Experimental / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D008115:Liver Regeneration; D008297:Male; D009336:Necrosis; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000199:Actins; D003893:Desmin; D004128:Dimethylnitrosamine