Introduction. Dust-induced lung pathology in miners is often combined with cardiovascular diseases such as coronary heart disease, hypertension, and atherosclerosis. In this regard, the search for ways to prevent the development of combined pathology with dust effects on the body is an urgent problem in occupational health.The aim of the study was to explore the effect of a complex preparation with dihydroquercetin on the level of protective proteins and myocardial morphostructure in the dynamics of dust-induced pathology development when inhaling coal-rock dust.Materials and methods. The study was conducted on white laboratory male rats weighing 200–250 g. The animals were divided into two groups: rats that inhaled coal-rock dust in the priming dust chamber daily for 4 hours for 1, 3, 6, 9 and 12 weeks; rats that received a daily complex drug with dihydroquercetin. The concentration of IL–6 proinflammatory cytokine and cardiomarkers (B-type brain natriuretic peptide, vascular endothelial growth factor, and fractalkin) was determined in the blood by enzyme immunoassay. In the cytosolic fraction of heart tissue, the level of expression of the hypoxia-induced transcription factor HIF — 1α, the inducible forms of proteins HSP72 and heme-oxygenase–1 was determined.Results. Prolonged dust exposure in the early stages (1–3 weeks) increased the expression of HIF–1α transcription factor and stress-inducible proteins — HSP72 and HOx–1 — in the myocardium. An increase in the dust exposure period of more than 6 weeks was accompanied by a decrease in the level of the HIF–1α transcription factor to control values, but the intensive synthesis of HSP72 and HOx–1 was maintained. In addition, the dynamics of long-term dust exposure to the body changed the level of cardiomarkers in the blood serum: 1) increased vascular endothelial factor; 2) fractalkin and IL–6 decreased in the early stages, as well as brain natriuretic peptide type B — the entire period of the study. By week 12 of dust exposure in the myocardial tissue it was revealed: dystrophic changes of a protein nature, signs of apoptosis, atrophy of some fibers and the development of diff use cardiosclerosis. Daily administration of a complex drug with dihydroquercetin to laboratory animals with prolonged exposure to coal-rock dust for 12 weeks led to the restoration of the level of protective cardiomarkers to control values and reduced the severity of morphological changes in the heart tissue.Conclusions. The administration of a complex drug with dihydroquercetin during prolonged dust exposure on the body has a cardioprotective effect, which is confirmed by the achievement of control levels of cell proliferation factors (B- type brain natriuretic peptide), angiogenesis (vascular endothelial factor), proinflammatory (IL–6) and anti-inflammatory response (CX3CL1), as well as a decrease in the severity of dystrophic changes in myocardial muscle fibers and almost complete disappearance of lymphocytic infiltration in heart vessels.Th e authors declare no confl ict of interests.
The aim of the study was to study the polymorphism of HIF-1A (rs11549465) and VEGFA (rs2010963) genes and their association with immunological parameters among the miners with lung dust pathology in the Kemerovo region. Material and methods. 200 Kuzbass miners aged from 39 to 58 years, working in the primary occupations with a high risk of occupational pathology, were examined. All the subjects were divided into two groups: the 1st group included 130 cases with a proven diagnosis of dust lung pathology. The 2nd group was a control one represented by 70 workers in the same sanitary and hygienic conditions but without occupational diseases. Polymorphisms of the HIF-1A (rs11549465) and VEGFA (rs2010963) genes were studied by the method of real-time polymerase chain reaction. Immunological parameters were determined by immunoenzyme (immunoglobulins A, M and G) and immunoturbidimetric (haptoglobin, ceruloplasmin and α-1-antitrypsin) methods. Results. The study of the distribution of heterozygous genotypes 1772C/T HIF-1A and -634G/C VEGFA did not reveal statistically significant differences between the miners with dust lung pathology and healthy individuals in the South of the Kemerovo region. However, the study results showed heterozygous polymorphisms HIF-1A and VEGFA, particularly the level of haptoglobin α-1-antitrypsin, ceruloplasmin, and IgM, to affect the mmune status of the miners with dust lung pathology. Conclusion. Heterozygous polymorphisms 1772C/T HIF-1A and -634G/C VEGFA can be used to determine the immune response and predict the development of dust lung pathology in miners, as well as the choice of treatment and preventive measures.
Introduction. Occupational dust pathology of respiratory organs in Kuzbass remains relevant due to its high prevalence among workers of the coal industry. Entering the body, the components of coal cause the development of pneumoconiotic fibrosis. Innovative ideas about the morphogenesis of fibrosis in recent years have shifted to the molecular level and appeal to the state of cellular receptors, the expression of some genes and the repression of others, a radical change in the cellular phenotype, which is the platform on which complex pathological processes occur. The study aims to research the mechanisms of fibroplastic changes in the lung tissue of miners from the position of epithelial-mesenchymal transformation. Materials and methods. The authors carried out histological and immunohistochemical studies of the respiratory system obtained during fifty autopsy operations of a group of Kuzbass miners working in underground. We studied the bronchial mucosa, respiratory lung tissue, arteries and veins of the small and large circulatory circles. The scientists perfomed immunohistochemical study using monoclonal antibodies (marker of proliferation Ki-67; oncogene of proapoptotic activity Bcl-2; endothelial function factors CD-31 and CD-34; marker of epithelial tissue cytokeratin; muscle tissue markers: actin, desmin, vimentin; connective tissue markers: type III collagen; muscle tissue collagenization marker: EMA; intercellular adhesion molecules E and N-cadherins; macrophage antigen (HAM5600)). Results. Epithelial cells of bronchi of coal industry workers partially lose the ability to express cytokeratins with the replacement of individual cell clusters with cells with non-core expression of maternal epithelial tissue of muscle antigens (vimentin, desmin, actin). When exposed to dust, the epithelial phenotype changes with changes in the quantity, shape and quality of the tissue structures of the lung tissue. Epithelial cells become elongated, fusiform, lose polarity and intercellular connections, acquire mobility and the ability to migrate beyond the tissue histione. Hyperactivation of cellular signaling pathways leads to disorganization and partial disintegration of the cytoskeleton with the appearance of functional mobility of cellular elements. A significant decrease in intercellular adhesive contacts under conditions of prolonged exposure to coal-rock dust leads to suppression of the expression of E-cadherin with partial substitution for N-cadherin contacts. Meanwhile, epithelial cells go through the process of epithelial-mesenchymal transformation, participate in the processes of fibrosis.Activated myofibroblasts are the main source of fibrosis in the lungs , their precursors can be both resident and bone marrow fibroblast-like cells. Dedifferentiated epithelial cells can act as decompensation of the regenerative capacity of lung tissue. Conclusion. The concepts of epithelial-mesenchymal transformation as a mechanism of the main pathological changes in pneumoconiosis should serve as a foundation for further in-depth study and understanding of the complex pathogenetic aspects of this problem in medicine. Ethics. The authors conducted all the studies of the dead miners with the help of a secondary examination of blocks and ready-made histological micro-preparations (glasses) of the material of the Bureau of Forensic Medical examination in Novokuznetsk, Osinniki, Prokopyevsk. The researchers carried out studies of pathomorphological material strictly on the basis of Federal Law No. 323-FZ of 21.11.2011 "On the basics of protecting the health of citizens in the Russian Federation", in particular Article 67 "Conducting pathoanatomic autopsies", Federal Law No. 8-FZ of 12.01.1996 "On Burial and Funeral Business" (Article 5, paragraph 1, 2), as well as in accordance with the Order of the Ministry of Health of April 29, 1994 No. 82 "On the procedure for conducting a pathoanatomical autopsy" (appendix to the order of the Ministry of Health and Medical Industry of 29.04.1994 No. 82), Order of the Ministry of Health of Russia of 24.03.2016 No. 179n "On the rules for conducting pathoanatomical studies".
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