EXPRESSION OF PROTEIN GENES PARTICIPATING IN FIBROPLASTIC PROCESSES IN MICE LUNG DURING THE DEVELOPMENT OF TUBERCULOUS INFLAMMATION
Peter Mikhaylovich KOZHIN1, Anton Vladimirovich CHECHUSHKOV1, Natal’ya Sergeevna ZAYTSEVA1, Marina Valer’yevna KHRAPOVA1, Liliya Aleksandrovna CHERDANTSEVA2,3, Elena Bronislavovna MENSHCHIKOVA1, Aleksandr Vasil’yevich TROITSKY1, Vyacheslav Alekseevich SHKURUPY2,4
1Research Institute for Experimental and Clinical Medicine of Federal Research Center
2Research Institute for
Experimental and Clinical Medicine of Federal Research Center
3Novosibirsk Research Institute of Traumatology and Orthopaedics n.a.
Ya.L. Tsivyan
4Novosibirsk State Medical University of Minzdrav of Russia
Keywords: туберкулезный гранулематоз, фиброз, окисленный декстран, декстразид, матриксная металлопротеиназа-9, проколлаген типа III, TGF-ОІ, ZEB1, Snai1, tuberculous granulomatosis, fibrosis, oxidized dextran, dextrazide, matrix metalloproteinase 9, type III procollagen, TGF-ОІ, ZEB1, Snai1
Abstract
The study analyzes the
expression of protein genes involved in intracellular signaling pathways
associated with a profibrotic response, activation of
epithelial-mesenchymal and endothelial-mesenchymal transitions, in
modeling tuberculous granulomatosis and pharmaceutical effects. Material
and methods. The study was performed on male BALB/c mice aged two
months and weighing 18-22 g. Generalized tuberculous granulomatosis was
simulated by a single intravenous (retro-orbital) injection of 0.5 mg
BCG vaccine in 0.2 ml of isotonic aqueous NaCl solution (SS), after 4
months a part of mice started to receive treatment drugs, after 2 months
the animals were sacrificed by decapitation (6 months after BCG vaccine
administration) and their lung tissues were collected. Mice were
divided into 6 groups, 5 males in each: intact, which were intravenously
into the retro-orbital sinus injected with 0.2 ml SS (C); infected with
BCG and receiving SS intraperitoneal injections (BS); infected with BCG
and received intraperitoneal injections of isonicotinic acid hydrazide
solution (INAH) (BI); infected with BCG and received intraperitoneal
injections of dextrazide solution (conjugate of 40 kDa oxidized dextran
and INAH) (BD); infected with BCG and received intraperitoneal or
inhalation injections of solution of molecular-nanosomal pharmaceutical
compositions of oxidized dextran (MNPC) (BMP and BMH, respectively).
Finally, the expression of mRNA of matrix metalloproteinase 9, type III
procollagen, TGF-β, and transcription factors ZEB1 and Snai1 was
determined by real-time PCR in mice lung tissue. Results. The modeling
of generalized tuberculous granulomatosis was found to be accompanied by
the induction of epithelial-mesenchymal transition and the activation
of profibrotic processes, which after 6 months was manifested in
increase of the type III collagen α1-chain and TGF-β mRNA expression.
Administration of traditional (INAH) and original (dextrazide, MNPC)
preparations with anti-tuberculosis activity within two months has
inhibitory activity of varying severity in relation to various markers
of these processes.
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