Marushchak M. Pathogenesis of the acute lung injury: violation of the oxidation, immune-cytokine, necrotic, and apoptosis-mediate processes.

The dissertation is dedicated to the examination of the pathogenesis peculiarity of the acute lung injury in male rats in consequence of the intratracheal administration of the hydrochloric acid based on the investigation of metabolic violation and destructive processes on the local and systemic levels. The conducted investigations showed that the main onset of the acute lung injury is the development of the hypoxia and the respiratory acidosis which is caused by the violation of the gases diffusion in the alveolus, and is led by the deviation on the regulatory level in the central and the peripheral circulatory dynamics. The respiratory acidosis, that was developed, conduce the protheolytic destruction of the lung tissue, in a result of what the peroxidation intensivity of the proteins and lipids that are the main endotoxemic factors. The defined direct dependence between the processes activation of the free radical oxidation, the depression of the antioxidant protection and the initiation of the inflammatory process and the destruction of the lung tissue during the acute lung injury. The acute lung injury changes the response of the cell and humorous components of the nonspecific resistance and immune system, which is evident 2 hours by the accurate enhancement after of the B-lymphocytes, serum immunoglobulin of the classes A and G, circulating immune complexes and after 12 hours by the enhancement of the total amount of the lymphocytes in the bronchoalveolar lavage with the phenotype CD4+ and CD8+. The hyperproduсtion of the proinflammatory ІL-1?, ІL-6 and ІL-8 in the bronchoalveolar lavage and the blood serum conduces the activation and the degranulation of the neutrophiles and the start of the metabolic cascade reactions, upon that the realization of the cell death is evident by the increase of the neutrophilic granulocytes destructive changes according to the late apoptosis or necrosis type during the first 6 hours of the injury with the following slowdown of these processes and the activation of the early apoptosis, that reaches its maximum after 24 hours of the acute lung injury, which confirms morphologically. Firstly it was determined the in the initiation of the apoptosis first stage in the setting of the acute lung injury play the system of the tumor necrotic factor alpha and products of the free radical oxidation reactions.