Уровень мРНК гена Nos2 как маркер фиброгенеза печени крыс, индуцированного тиоацетамидом

Abstract

The aim of this paper was to evaluate the potential of the mRNA level of the Nos2 gene as a marker of fibrogenesis in rats at different stages of thioacetamide-induced liver fibrosis and cirrhosis. Materials and methods. The experiment involved 117 mature male Wistar rats weighing 190–210 g. Liver fibrosis and cirrhosis were induced by a thioacetamide solution administered through a gastric catheter at a dose of 200 mg per 1 kg of body weight 2 times a week. The dynamics of the process was studied at 9 timepoints over the course of 17 weeks. Nos2 mRNA level in the liver was detected by means of real-time polymerase chain reaction. The stage of fibrosis was determined in histological sections stained using the Mallory method according to the Ishak semi-quantitative scale. Results. Throughout the experiment, Nos2 mRNA had practically no reaction to the thioacetamide-induced liver fibrogenesis. At the mild fibrosis stage (F1), an insignificant rise in the level of Nos2 mRNA was noted (within 5 %). Intensive development of fibrosis (F2–F4/F5) and an increase in the production of extracellular matrix components were accompanied by an increase in the level of Nos2 mRNA with a peak value exceeding the initial level (control group value) by the factor of 1.69 (р < 0.05). At the point of transition of fibrosis to cirrhosis (F5), a decrease in the level of mRNA of the target gene was observed, and at the stage of definite cirrhosis (F6), a subsequent drop below the initial level was detected. Thus, according to the data obtained, Nos2 mRNA has the greatest potential as a marker of liver fibrogenesis at the stage of advanced fibrosis, but cannot act as a marker at the early stages. Moreover, Nos2 mRNA level cannot be used as a marker when assessing the degree of cirrhosis and its development dynamics.