The dissertation is devoted to the establishment of pancreatic damage mechanisms with a negative effect on the mother-fetus system of unbalanced nutrition and chronic stress by in-depth study of its morphological and functional state, balance of regulatory cytokines, oxidant-antioxidant homeostasis (OAH), biogenic elements (BE) in pancreatic tissue and serum blood. The experimental study was conducted on 67 randomly bred female rats of the Wag / g Sto population of 4.5-5 months of age and their offspring in the amount of 299 individuals. In mother rats, unbalanced nutrition and chronic stress entail violations of the morphofunctional state of the pancreas: changes in the relative area of the parenchyma and acinus area, atrophy of the parenchyma, edema of the connective tissue, the development of inflammation, plethora of the stroma, intra- and interlobular sclerosis and lipomatosis, dystrophic phenomena in exo- and endocrinocytes, neoplasm of small islets of Langerhans, a change in their average area and the number of ?- and ?-cells in them. In the newborn, 1-month and 2-month-old offspring of females of all groups, in general, the morphological changes in the pancreas are similar to those of their mothers. In addition, there are signs of immaturity of the parenchyma and stroma, periductal pancreatofibrosis. The most pronounced disorders occur with nutrient deficiencies. 100% of mother rats of all groups and their offspring have a systemic humoral response to pancreatic damage in the form of an imbalance of regulatory cytokines (interleukins 12 and 4), which, in turn, has a negative effect on the pancreas. A significant increase in the serum level of the marker cytokine of Th1 lymphocytes (interleukin 12) and a decrease in the level of marker cytokine of Th2 lymphocytes (interleukin 4) is evidence that the immune response to pancreatic damage is realized by activation of cellular immunity reactions against the background of a decrease in the activity of the humoral response reactions. The severity of cytokine imbalance (an increase in the ratio of interleukins 12 and 4) in general is higher in the offspring than in their mothers. An unbalanced diet and chronic stress of females during pregnancy entails a violation of the oxidant-antioxidant homeostasis in both the mother rats themselves and their offspring. Normal oxidant-antioxidant homeostasis occurs in the pancreas tissue of animals (a combination of the normal level of lipid peroxidation (LPO) activity and the antioxidant system - AOS) and four variants of its violation: 1) increased uncompensated lipid peroxidation activity (increased lipid peroxidation activity with a decrease or increase in antioxidant system activity); 2) increased hypercompensated (pseudo-low) lipid peroxidation activity (decreased lipid peroxidation activity with an increased level of antioxidant system activity); 3) increased hypercompensated (pseudo-normal) lipid peroxidation activity (normal level of lipid peroxidation activity with increased antioxidant system activity); 4) decreased lipid peroxidation activity (decreased lipid peroxidation activity with a low level of antioxidant system activity). In general, the greatest degree of oxidant-antioxidant homeostasis disturbance is observed in mother rats of all groups and newborn rats whose prenatal development occurred in conditions of excess or deficiency of nutrients. In the blood serum of experimental animals, normal oxidant-antioxidant homeostasis occurs (a combination of a normal level of lipid peroxidation and antioxidant system activity) and three types of violation of oxidant-antioxidant homeostasis: 1) increased uncompensated lipid peroxidation activity (increased lipid peroxidation activity with a decrease in antioxidant system activity); 2) increased compensated lipid peroxidation activity (increased lipid peroxidation activity with adequate activation of antioxidant system); 3) increased hypercompensated (pseudo-normal) lipid peroxidation activity (normal level of lipid peroxidation activity with increased antioxidant system activity). In general, the greatest degree of oxidant-antioxidant homeostasis violation is observed in 1-2-month-old rats whose prenatal development occurred in conditions of deficiency of energy substrates and gestational stress. The effect of unbalanced nutrition and chronic stress on the mother-fetus system in maternal rats and their offspring leads to a violation of the balance of BE in the pancreatic tissue and blood serum with a predominant decrease in their content in the noted biological media. Despite the heterogeneous changes in the level of biogenic elements as a whole, there is a pattern in the direction of deviations from the control values of biogenic elements in the pancreatic tissue, which consists in a decrease in the level of calcium and magnesium in mother rats that received hypercaloric nutrition, and their offspring, and a decrease in the content of zinc and copper in mother rats receiving hypocaloric nutrition and suffering chronic stress, and their offspring; in serum, a steady decrease in the level of magnesium is observed in females who had a deficiency of nutrients, and their offspring, zinc and copper in animals of the same groups, as well as mother rats that suffered chronic stress, and their offspring. It was established that changes in the oxidant-antioxidant homeostasis and the level of biogenic elements in the pancreas tissue and blood serum of animals under the conditions of the negative influence of unbalanced nutrition and chronic stress on the mother-fetus system are not identical, which manifests their organ-specificity and relative informativeness of the results of the study of blood serum for determining oxidant-antioxidant homeostasis and biogenic elements balance in pancreatic tissue. An imbalance of regulatory cytokines, disturbance of oxidant-antioxidant homeostasis and biogenic elements balance are important links in the pathogenesis of damage to the pancreas of mother rats and their offspring under the influence of negative exogenous factors on the mother-fetus system.
