Raikevych V. Experimental substantiation of the use of PRP-therapy in the treatment of trophic ulcers

The dissertation is devoted to addressing a relevant task of experimental pathophysiology, namely establishing the pathogenetic patterns of systemic and tissue disorders in experimental skin trophic ulcer in rats and providing a scientific rationale for the efficacy of local application of platelet-rich plasma (PRP) as a pathogenetically targeted method for correcting the identified impairments. On a single experimental model of mechano-chemical trophic ulcer in rats, a complete temporal and pathogenetic sequence of systemic disorder development was established, with detailed kinetics of their resolution or chronicity: The existence of a "skin – endotoxicosis – liver" pathogenetic axis was proven, supported by the chronological coincidence of the peak of systemic endotoxicosis (maximum erythrocyte intoxication index and lipid peroxidation) with the peak of hepatocyte cytolysis syndrome. Differential elimination kinetics of endotoxins and immune complexes were established, wherein MSM₂₅₄ normalization is accompanied by persistently elevated MSM₂₈₀ levels even on day 28 of untreated pathology. The chronology of the humoral immune response under conditions of a prolonged wound process was elucidated: an early peak of IgG precedes the delayed hyperactivation of IgA and IgM on day 14. A chronological gap between oxidative damage and enzymatic defense was demonstrated: critical depletion of reduced glutathione precedes the maximum compensatory hyperactivation of superoxide dismutase and catalase. A comprehensive comparison of biochemical markers was carried out with parallel morphological monitoring of three target organs simultaneously (skin, liver, and kidneys). It was proven that focal destructive skin injury without treatment leads to progressive systemic visceral damage-necrobiotic changes in hepatocytes and destruction of the renal tubular apparatus with loss of the brush border. The multi-target corrective effect of PRP therapy was quantitatively proven and morphologically verified: accelerated epithelialization and restoration of a full-fledged collagen matrix and skin appendages; suppression of endotoxicosis and rapid elimination of inflammatory proteolysis; and hepato- and nephroprotective effects of local PRP application with restoration of hepatic trabecular histoarchitecture, normalization of transaminase levels, and regeneration of renal tubular epithelium. Using mathematical correlation and regression analysis, the pathogenetic unity of impairments among lipid peroxidation, endotoxicosis, and enzymatic links (r = 0.86–0.93) was statistically objectified, and a regression model for predicting the state of the glutathione reserve based on malondialdehyde levels was constructed. The scientific concept regarding the feasibility of utilizing platelet-rich plasma biotechnological products as a multi-component pathogenetic method for treating chronic wounds-capable of synergistically correcting both local regenerative processes and systemic visceral complications-has been further developed.