MORPHOLOGICAL MONITORING OF EXPERIMENTAL LIVER FIBROSIS IN RATS

Abstract

Background. Though thioacetamide (TAA)-induced liver fibrosis (LF) is recognized as a classical model of toxic liver damage, there is no literature data on the description of its successive stages of histological and ultrastructural changes in various cell populations involved in fibrosis. Objective. To conduct morphological monitoring of fibrosis formation in the liver of rats using the TAA model of LF based on histological and ultrastructural changes in hepatocytes and perisinusoidal lipocytes (HSC). Material and methods. The experiment was carried out on 18 sexually mature male rats. LF was modeled by intraperitoneal injection of 2% TAA solution at a dose of 10 ml / kg every other day. Light microscopy of semi-thin sections of the liver was performed, as well as electron microscopy of ultrathin sections. Results. The study of semi-thin sections of rat liver tissue from the control group showed a normal architecture of the parenchyma, a large number of HSCs containing large lipid droplets ("resting" phenotype), a very small amount of cytoplasmic matrix poor in membrane organelles. In the animals that were receiving TAA for 4 weeks, a mesenchymalepithelial transition of HSCs from the "resting" type to a fibrogenic state (fibrogenic phenotype) was recorded, that was accompanied by a gradual decrease in the number of retinol-containing drops and the appearance of fibroblastlike cells (FLC) in HSCs. In the animals, that were receiving TAA for 12 weeks, the pool of fibrogenic cells in the liver increased, a mesothelial-mesenchymal transition occurred, characterized by the mesothelial cell migration deeper into the parenchyma and their acquisition of a mesenchymal phenotype. Lipid containing activated FLC were also found in fibrous tissue around the central vein. Foci of hepatic tissue destruction caused by necrosis and apoptosis of hepatocytes were much more common. Conclusions. Administration of TAA induces liver fibrosis while histological and ultrastructural monitoring of the state of hepatocytes and HSCs allows to monitor all stages of fibrosis, clarifying the mechanisms of damage to intracellular organelles and variants of hepatocyte death. This model of LF in rats can be used to test new antifibrotic drugs.