Persistence of Liver Cirrhosis in Association with Proliferation of Nonparenchymal Cells and Altered Location of α-Smooth Muscle Actin-Positive Cells

Abstract

This study was carried out to achieve pathological understanding for the persistence of cirrhosis induced by thioacetamide (TAA). Forty-five, male, 21-day-old, F344 rats were randomly allocated to group 1 and received drinking water as a control, and groups 2 and 3 given 0.015% or 0.03% TAA, respectively for 12 weeks. Two-third of animals per group were sacrificed, and remainder were maintained for a further 4 weeks without TAA treatment. Liver cirrhosis was induced in all animals in group 3 at week 12, with obvious increase of collagen content, and this persisted after cessation of TAA. Proliferating cell nuclear antigen (PCNA) positive labeling indices of nonparenchymal cells were increased significantly after cessation in groups 2 and 3 ( p < 0.01). RT-RCR analysis of α-smooth muscle actin ( α-SMA) showed significant increase in group 3 compared to that of control at both time points ( p < 0.05). Immunohistochemical staining of it demonstrated positive cells to mainly be located around regenerating hepatic nodules at week 12, however, they were focused into enlarged portal areas consisting of fibrous tissues and pseudo-bile ductular cells after the cessation. Taken together, we conclude persistence of liver cirrhosis could be associated with the proliferation of nonparenchymal cells and altered location of α-SMA positive cells.