Motorna N. Morphological changes of the liver against the background of reactivation of herpes simplex virus type 1 with impaired cerebral circulation (experimental study)

The dissertation examines the structural changes of the liver against the background of infection caused by herpes simplex virus type 1, evaluates cytopathological changes in hepatocytes, and studies the development of changes in blood vessels of the lobular microcirculation, hepatocyte damage in acute and delayed periods and after stroke simulation. Stroke-induced reactivation of herpes simplex virus type 1 was established in animals carrying latent infection. Morphological and morphometric features of hepatocyte damage and regeneration, which coincide with the viral decrease in HSV-1 titer in the serum and tissues of the studied samples, have been established. It was found that in the acute period the focal cytopathological changes of hepatocytes dominate, and diffuse-focal dominate in the remote period. Verification of cytopathological changes of hepatocytes according to the morphology of the nucleus was performed. It was found that the redistribution of hepatocytes with nuclear hypertrophy, atypical and lytic nuclei may be a criterion for the dynamics of cell damage or death. Against the background of the infectious process, the absence of reactive reactions (migration and degranulation) of mast cells was revealed, which allowed us to conclude about the negative impact of herpes simplex virus type 1 on these liver cells. It was discovered that stroke is not only a factor of systemic changes in microcirculation, but also a factor in reactivation of systemic herpesvirus infection. Disorders in the vessels were edema of endothelial cells, their death and desquamation into the lumen, violation of the integrity of the basement membrane and diapedesis of blood cells in the subendothelial space. The presence of virions in the cytoplasm of endothelial cells was registered by electron microscopy, which proves the polytropy of the virus and the role of vascular endothelium as an independent source of virus reproduction and factor of penetration of the virus into the liver after stroke. The absence of virions in the hepatocytes of the liver allowed us to conclude about the rapid reproduction and elimination of the virus from hepatocytes. Based on the detected ultrastructural changes in the cytoplasm of hepatocytes, which consisted in the accumulation of a significant density of osmophilic granules, lysosomes and lamellar cells, the consequences of the infectious process at the subcellular level were assessed. According to virological studies (PCR and ELISA) and the Vero cell culture method, a decrease in the level of HSV-1 infection titer from the 5th to the 30th day after infection and a subsequent increase in this indicator after stroke simulation were determined. These data prove the suppression of acute viral infection in the long term and its activation on the background of cerebrovascular disorders. According to the results of histological research, a decrease in the level of dystrophic changes of hepatocytes of the liver during pharmacological correction of herpes infection with antiviral drugs in stroke in animals infected with herpes simplex virus type 1 was established. The method of flow cytometry revealed changes in the redistribution of peripheral blood leukocytes in HSV-1 in the direction of granular leukocytes and the production of reactive oxygen species (ROS) by agranulocytes. Stroke on the background of herpesvirus infection caused changes in the ratio of leukocytes to granulocytes, characterized by a sharp decrease in phagocytosis and ROS-producing function, and a reduced number of agranular leukocytes did not differ from the control of phagocytic number. It was proven for the first time that stroke has a significant negative impact on immune status and even pharmacological correction of the infectious process does not affect the restoration of functional activity of peripheral blood leukocytes, i.e. the formation of an immunosuppressive state.