SYSTEM MATRIX METALLOPROTEINASE/INHIBITORS IN PATHOGENESIS OF INFILTRATIVE PULMONARY TUBERCULOSIS, DEPENDING ON THE RESISTANCE OF MYCOBACTERIUM TUBERCULOSIS STRAINS FOR ANTI TUBERCULOSIS THERAPY

DOI: https://doi.org/10.29296/24999490-2023-03-07

D.S. Esmedlyaeva(1), N.P. Alekseeva(2), M.E. Dyakova(1)
1-St. Petersburg State Research Institute of Phthisiopulmonology of the Ministry of Healthcare of the Russian Federation,
Ligovsky Prospekt, 2–4, St. Petersburg, 191036, Russian Federation;
2-St. Petersburg University, Universitetskaya emb., 7/9, St. Petersburg, 199034, Russian Federation

Introduction. The search for molecular markers of adverse treatment outcomes in individuals with pulmonary tuberculosis (PT) is relevant due to the worldwide increase in drug resistance of Mycobacterium tuberculosis (MBT) strains to anti-tuberculosis drugs (PTP). Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) they are markers of destruction and remodeling. The aim of the study. To study the features of the levels of the MMP in patients with infiltrative PT (IPT), depending on the MBT to PTP. To determine their significance as molecular markers of the effectiveness of therapy. Methods. The concentrations MMP-1,-3,-8,-9 and TIMP-1 were measured using the ELISA method, kit «R&D Systems» (Minneapolis, MN, USA), the activity of α2-macroglobulin, neutrophils elastase (EL) – enzyme assays in the blood serum of 115 patients with ITL (58 drug – sensitive and 57 DR MBT). The effectiveness of the intensive phase of treatment was evaluated retrospectively. We used Statistica 10.0 (StatSoft, Inc.) and R. Results. Regardless of the DR of MBT strains, patients with ITL have an imbalance in the MMP/inhibitors system towards proteinases. Regardless of the DR, the changes in circulating levels of MMP, TIMP-1 and EL were unidirectional with the otal volume of focuses and decay, as well as the number of neutrophils. Combinations from proteinase with results of chest X-rays methods of research at baseline levels in patients with ITL can be molecular prognostic markers of treatment outcomes. Conclusion. The methods of multidimensional statistics showed that changes in the baseline levels of the MMPs and inhibitors in patients with ITL are not associated with the characterization of the resistance of MBT strains to the PTP, but are an objective criterion for the activity and prevalence of a specific process, and combinations from the MMP reflect the direction of its changes.
Keywords: 
a pulmonary tuberculosis, matrix metalloproteinases, matrix metalloproteinase inhibitors, drug-resistant tuberculosis, biomarkers
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