The role of perlecan in remodeling the extracellular matrix of the liver, lungs and spleen of mice after administration of BCG vaccine and the liposome-encapsulated dextrazide

Abstract

Despite significant advances in the diagnosis of tuberculosis, the issues of the mechanism of development and treatment of fibrotic manifestations are relevant and take place in the treatment. The aim of the study was to study the content of perlecane and to find out its participation in the remodeling of the extracellular matrix of the organs of mice with tuberculous inflammation and when they were injected with an antitubercular composition. Materials and methods. The experiment was carried out on male mice of the BALB/c line, which were divided into 4 groups of 5 individuals each. All animals, with the exception of intact mice (group 1), were retroorbitally injected with BCG vaccine once (0.5 mg of microbial bodies in 0.2 ml of 0.9% NaCl solution) to simulate a generalized tuberculosis process. After infection 6 mo for 3 mo, group 2 mice were intraperitoneally injected with 50 µl of 0.9% NaCl solution, group 3 - intraperitoneally with 50 µl of liposome-encapsulated dextrazide solution (LEDZ, isoniazid conjugate and oxidized dextran enclosed in liposomes), group 4 - LEDZ solution was inhaled by spraying in the chamber through a nebulizer for 5 min at the rate of 50 µl of solution per animal. After the last administration of the NaCl and LEDZ solution, mice were removed from the experiment, organs were taken, and tissue homogenates were prepared. The content of perlecane, hyaluronan, protein-bound hydroxyproline, tissue metalloproteinase inhibitors (TIMP-1, TIMP-2) and the activity of matrix metalloproteinases (MMP), hyaluronidases, α2-macroglobulin were measured. Results. In all organs of infected mice, the content of perlecan, hyaluronan, protein-bound hydroxyproline, TIMP-1, TIMP-2 was increased, MMP, hyaluronidase, α2-macroglobulin were activated. Regardless of the method of administration of LEDZ, the severity of fibrosis decreased due to a decrease in the content of hyaluronan in all organs and protein-bound hydroxyproline in the lungs. Perlecan with intraperitoneal administration is involved in fibrosis of the spleen, inhalation - reflects the severity of liver fibrosis. Conclusion. Correlations of perlecan with extracellular matrix components reflect participation in the regulation of fibrosis of organs in BCG-induced inflammation.