Test object: hemostasis mechanisms in health state and in peptic ulcer.Goal of the study: investigation of mechanisms of erythrocyte and leukocyte participation in blood coagulation in health state and in stomach ulcer.Investigation methods: experimental modeling of peptic ulcers; pathophysiological, hemocoagulational, hematological, biochemical, pharmacological, microbiological, morphological, and statistical methods.Scientific novelty of the obtained results. Ability of intact erythrocytes for activation of internal thromboplastin formation in the conditions of platelet-derived factor 3 deficiency has been studied and proven for the first time. This ability, unlike similar ability of platelets, is preserved in the conditions of decreased activation of Hageman factor. We have established that activating effect of intact erythrocytes on internal thromboplastin formation is related to the presence of thromboplastin factor of erythrocytes, presenting a glycolipoproteid of molecular weight 17,540-22,590, located in D fraction of erythrocyte stroma, and possessing properties of tissue thromboplastin (factor III) of platelets. The mechanism of inclusion of thromboplastin factor of erythrocytes into thromboplastin formation process has been established; it consists in preservation of cellular membrane external layer sialoproteid, acting as a certain mediator between thromboplastin factor of erythrocytes and activated plasma coagulation factors. High molecular stromal proteins (167,900), accelerating fibrinogen transformation into fibrin and resembling factor 2 of platelets by their biological effect, were found in fraction A of erythrocyte stroma. Mechanism of erythrocyte participation in hemostasis system, consisting in activation of endogenous A2 phospholipase, destabilization of erythrocyte membrane lipid structures, accumulation of free fatty acids, change in quantitative ratios between separate fractions in phospholipid composition, and cholesterol loss by cellular membranes, has been determined for the first time. Phospholipids of internal layer of erythrocyte membrane, phosphatidylethanolamine and phosphatidylserine, have been proven to accelerate blood coagulation process, while phospholipids of outer biolayer side, sphingomyelin and phosphatidylcholine, have been proven to inhibit blood coagulation. Active participation of leukocytes in cellular aggregation reactions and their inclusion into primary hemostatic plug has been shown; leukocytes are able to activate coagulation hemostasis due to the presence of thromboplastin, anti-heparin, and fibrin-stabilizing factor in them. The processes of free-radical lipid oxidation in erythrocytes and activity of antioxidant enzymes in erythrocytes in Okaba’s experimental peptic ulcer were studied for the first time. Activation of lipid peroxidation in erythrocytes and decrease in activity of basic erythrocyte antioxidant enzymes, catalase and reduced glutathione, has been shown to determine the increase of aggregative activity, decrease of peroxide resistance and erythrocyte ability for deformation, as well as increase of erythrocyte suspension viscosity in peptic ulcer. Application of antioxidant Melaxen in treatment of peptic ulcer has been pathogenetically substantiated for the first time on the model of chronic peptic ulcer. The mechanism of its reparative effect, based on inhibition of necrotic processes development in stomach mucous tunic and stimulation of recovery according to restitution type in case of defects has been established, which included complete restoration of mucous tunic due to restoration of number of proteins of molecular weight 89, 95 and 99 kDa, formation of new protein fraction of molecular weight 36 kDa, normalization of cholesterol content, increase of triacylglyceride level and basic prospholipid fractions level, phosphatidylinositol and phosphatidylethanolamine, in cells of stomach mucous tunic. Melaxen inclusion into standard therapy of patients with peptic ulcers has been pathogenetically justified – this treatment promotes rapid scarring of ulcer and prevents its recurrence.Theoretical and practical value of the obtained results. This study belongs to basic investigations. The obtained results prove erythrocyte and leukocyte participation in hemostasis system in health state and in stomach ulcer, and generally broaden the concepts of blood coagulation processes and pathogenesis of peptic ulcer. The results of the study can be used as pathogenetic justification of antioxidant inclusion into complex scheme of peptic ulcer treatment. In particular, high antiulcer activity of Melaxen (17.5) and its positive effect on reparation processes in stomach mucous tunic due to restoration of protein quantity, normalization of cholesterol content, increase of triacylglyceride level and basic prospholipid fractions level, phosphatidylinositol and phosphatidylethanolamine, in cells of stomach mucous tunic has been shown. Implementation degree: the thesis results were implemented in academic activity in the departments of pathological physiology of National Pharmaceutical University, Kharkov; “Ukrainian Medical Dental Academy” HSEU, Poltava; Zaporozhie State Medical University; Donetsk National Medical University; N.I. Pirogov Vinnitsa National Medical University; Bukovina State Medical University, Chernovtsi; Ivano-Frankovsk National Medical University; V.V. Podvysotsky department of general and clinical pathophysiology of Odessa State Medical University.
