Sarakhan V. Pathogenetically substantiated correction of endothelial dysfunction in diabetes mellitus aimed at prevention of microcirculatory complications

The thesis is devoted to the complex research of pathogenetic links of late diabetic complications, as well as to the development of pathogenetically substantiated effective method of correction of these nosological conditions. A comprehensive approach to the study of the mechanisms of endothelial dysfunction formation and its role in hemodynamic and biochemical disorders in the kidneys on the background of type 2 diabetes mellitus has been developed. It has been established the systemic nature of oxidative stress and disorders associated with changes in nitric oxide homeostasis under these conditions, the pathogenetic basis of which is endothelial dysfunction. It has also been proven that one of the key links in the development of diabetic nephropathy is the change in the levels of the cytokine profile and acute phase blood proteins. Hyperersistinemia has been shown to be associated with elevated levels of C-reactive protein and fibrinogen. Type 2 diabetes is the pathogenetic basis for increasing the level of resistin and acute phase proteins. The detected changes in the enzymatic activity of erythrocytes in rats with diabetic nephropathy are largely due to shifts in inducible NO synthase. The results of experimental studies allowed to establish the participation of disorders of nitric oxide metabolism, oxidative stress, as well as pro-inflammatory cytokines and acute phase proteins in the mechanisms of microvascular complications on the background of type 2 diabetes; to develop a new methodological approach aimed at restoring endothelial function, inhibition of proinflammatory cytokines and acute phase proteins, as well as balancing the system of antioxidant protection and lipid peroxidation, which is used as adjunctive therapy with bioflavonoids in combination with L-arginine for 30 days.