Revenko O. Age-related aspects of the physiological role of the mesentery and its adipose tissue under stress (experimental study)

Oleh Viktorovych Revenko. Age-related aspects of the physiological role of the mesentery and its adipose tissue under stress (experimental study). – Qualifying scientific work as a manuscript. A thesis for obtaining the scientific degree of a Doctor of Philosophy majoring in 222 Medicine, a field of study 22 Healthcare. – Danylo Halytsky Lviv National Medical University, MoH [Ministry of Health] of Ukraine, Lviv, 2022. The thesis is devoted to the study of the physiological role of the mesentery and its adipose tissue in terms of age under a high-calorie high fructose diet, acute stress induction, and their combined impact, as well as to the study of the bioregulatory influence of hydrogen sulfide (H2S) on the preservation of mesenteric intactness while modeling damages of various origin. The peculiarities of the ultramicroscopic structural organization of mesenteric elements within normal limits and patterns of its transformation when aging, and in terms of acute stress induction in rats of various ages were first studied. When studying the age-related differences of morphofunctional ultrastructural organization of mesentery and its cellular elements using electron microscopy, it has been determined that old rats as compared to adult rats presented signs of degenerative changes of mesenteric adipocytes, fragmentation of large lipid droplets, the occurrence of defect mitochondria of various shape, and detected signs of ultrastructural changes in mesenteric microvessels and presence of destructively changed fibroblasts. Complex morphofunctional studies of mesenteric tissue and its components through electron microscopy were first conducted in terms of determining the peculiarities of the age-related changes under conditions of a combined influence of a 4-week high fructose diet and acute stress induction. The animals with patterns of damage induced by a 28-day high fructose diet (HFD) developed the cytolytic changes of mesenteric cells, being more marked in old rats as compared to adult rats. The specific features of the mentioned changes were represented by degeneratively changed, hypertrophic, and hyperplastic mesenteric adipocytes with damaged mitochondria of various shapes, endothelial dysfunction and the presence of disorganized connective tissue. The influence of acute stress detected the age-related differences in adaptation and compensatory mechanisms of mesenteric tissue components with its increased sensitivity to cytolytic influence in old rats being on an HFD. The increased level of TBARS in blood serum for 40% was found in old rats as compared to adult rats (p<0.05) when conducting an age-based comparison. The increased level of TBARS for 12-15% was detected in both age groups being on an HFD as compared to similar age groups on a standard diet (p<0.05). The results evidence the development of the oxidative stress induced by impaired oxidation-reduction equilibrium and cytolytic damage to the mesentery and its components. The mentioned changes can subsequently trigger the impairment of metabolic health. The age-related differences of Н2S role in adaptation and compensatory reactions of mesenteric tissue of rats under conditions of a 4-week high fructose diet, acute stress induction, and exogenous infusion of hydrogen sulfide synthesis donors were first studied. The influence of the exogenous H2S donors on the level of thiobarbituric acid reactive substances (TBARS) in blood serum and activity of cystathionine γ-lyase enzyme (CSE), cystathionine β-synthase (CBS), sulfite oxidase (SO), and thiosulfate sulfurtransferase (TST) in mesenteric tissue homogenates in rats of various age has been determined.