Kuznetsova M. Mechanisms of influence of unbalanced diet and chronic stress on the morphofunctional state of the liver in pregnant rats and their offspring

Українська версія

Thesis for the degree of Candidate of Sciences (CSc)

State registration number

0421U102251

Applicant for

Specialization

  • 14.03.04 - Патологічна фізіологія

21-04-2021

Specialized Academic Board

Д 64.600.03

Kharkiv National Medical University

Essay

The purpose of the study was to clarify the effect of a long-term diet with an excess and deficiency of nutrients, as well as chronic stress on the morphofunctional state of the liver in female rats and their offspring with respect to their age. To achieve the goal, we assessed the morphofunctional state of the liver in mother rats and their offspring (newborns, 1- and 2-month-olds) under conditions of prolonged stress and alimentary factor during pregnancy using pathophysiological, morphological, biochemical, immunohistochemical, analytical, and statistical methods. The study was conducted as part of an experiment in which 190 sexually mature random-bred WAG-population rats of reproductive age were used. Before the beginning of the experiment, 4 experimental groups were formed. Group 1 rats were the control. Rats of group 2 received a diet with an excess of nutrients (25% increased content of proteins, fats, and carbohydrates, and 20% solution of fructose instead of water) two weeks before male transfer and throughout the pregnancy. Rats of group 3 received a diet with a deficiency of nutrients (40% reduced content of proteins and carbohydrates) two weeks before male transfer and throughout the pregnancy. Rats of group 4 were kept under conditions of chronic stress (immobilization in plastic tight cage containers at different intervals and at different times to prevent adaptation to the stress factor) throughout the pregnancy. The data obtained as a result of the study allowed to establish the pathogenesis of morphofunctional state disorder development in the liver of mother rats and their offspring under the influence of chronic stress and a diet with an excess and deficiency of nutrients. The study showed that the long-term impact of stress and alimentary factor on rats’ organisms in the mother-fetus system causes significant disorders of the morphofunctional state of the liver at the organ, tissue, cellular, and subcellular levels. These disorders persisted in young rats up to month 2 of their life. Over time, the severity of disorders decreased. There were changes in the processes of cellular renewal and differentiation, as well as changes in the functioning of liver structures. Morphological rearrangements of its structural components were determined. Morphological changes were accompanied by changes in metabolic parameters in the liver: the development of protein metabolism disorders in the form of dysproteinemia, lipid metabolism disorders – hyperlipidemia, as well as carbohydrate metabolism disorders – development of hyperglycemia and hyperketonemia were established. When studying the morphofunctional state of the liver of the offspring born from female rats who received a diet with an excess of nutrients, it was found that it had almost no effect on the structure of the organ in the offspring. However, biochemical studies revealed some functional changes, which were the development of dysproteinemia, hyperlipidemia, which in turn was characterized by an increase in LDL, VLDL, and TG, as well as the development of hyperglycemia. A long-term effect of the diet with a deficiency of nutrients negatively affected the morphofunctional state of the liver of the offspring. This effect was the development of a pronounced discomplexation of the beam-radar structure, an increase in SPI by 20% (p<0.0001) due to an increase in stromal and parenchymal components of the liver and a decrease in the expression of endothelial synthase (newborns and 1 month old rats). Chronic immobilization stress also negatively affected the structural and functional state of the liver. This was a pronounced discomplexation of the beam-radial structure, an increase in SPI by 40% (p<0,0001) due to an increase in the relative volume of the stroma and a decrease in the expression of endothelial synthase. A more detailed study of the functional state of the liver revealed a lipid synthetic dysfunction of the organ, which included signs of impaired synthesis, secretion and reuptake of lipids. Thus, it is possible to conclude that prolonged exposure to stress and alimentary factors causes distinct changes in the morphofunctional state of the liver of both, female rats and their offspring (kept up to two months of age). The most severe disorders were caused by the action of chronic immobilization stress and the use of a diet with a deficiency of nutrients. The obtained data suggest that these factors can cause the development of a severe organic liver disease, namely fatty hepatosis, fibrosis, and portal cirrhosis, and various diseases, such as type 2 diabetes, atherosclerosis, etc.

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