Особенности ремоделирования внеклеточного матрикса печени и легких мышей с БЦЖ-гранулематозом в периоде хронического воспаления в зависимости от способа введения липосомальной формы декстразида

The objective: to study the effect of liposomal oxidized dextran (LOD) on remodeling of the extracellular matrix of organs of mice during the period of chronic BCG granulomatosis and effects of LOD on this process depending on the route of administration.Subjects and Methods. The liver and lungs of mice with BCG granulomatosis were studied using different methods of LOD administration (intraperitoneally and by inhalation). The content of glycosaminoglycans, hydroxyproline fraction, the activity of matrix metalloproteinases (MMPs), hyaluronidases and a2-macroglobulin, and the content of tissue inhibitors of MMPs (TIMP-1 and -2) were evaluated.Results. The administration of LOD to mice infected with the BCG vaccine suffering from chronic granulomatosis with severe fibrosis (6 months after infection for 3 months) resulted in the aggravation of collagen degradation in the liver. In the lungs, along with increased collagen degradation, decreased collagen synthesis was observed. It was apparently due to suppressed activity of a2-macroglobulin and decreased content of TIMP-1 and -2. In the liver, with intraperitoneal administration of LOD, signs of suppressed fibrogenesis and fibrolysis were observed versus the data obtained for inhalation administration. There were no differences in the content of hydroxyproline fractions in the lungs depending on the method of LOD administration. Thus, administration of LOD to mice led to lower severity of fibrosis while the mechanisms of fibrolysis in the lungs and liver differed.Цель: изучить влияние липосомальной формы декстразида (ЛФДЗ) на ремоделирование внеклеточного матрикса органов мышей в периоде хронического БЦЖ-гранулематоза и эффекты ЛФДЗ на этот процесс в зависимости от способа введения.Материалы и методы. Исследовали печень и легкие мышей с БЦЖ-гранулематозом при разных способах введения ЛФДЗ (интраперитонеально и ингаляционно). Оценивали содержание гликозаминогликанов, фракции гидроксипролина, активность матриксных металлопротеиназ (ММП), гиалуронидаз и а2-макроглобулина, содержание тканевых ингибиторов ММП (ТИМП-1 и -2).Результаты исследования. Введение ЛФ ДЗ мышам, инфицированным вакциной БЦЖ, в периоде хронического гранулематоза с выраженным фиброзом (через 6 мес. после инфицирования в течение 3 мес.) привело к усилению процесса деградации коллагенов в печени. В легких, наряду с усилением процесса деградации коллагенов, наблюдали снижение их синтеза. Этим процессам способствовали, по-видимому, подавление активности а2-макроглобулина и снижение содержания ТИМП-1 и -2. В печени при интраперитонеальном введении ЛФДЗ наблюдали признаки ослабления фиброгенеза и фибролиза относительно данных при ингаляционном введении. В легких различий в содержании фракций гидроксипролина в зависимости от способа введения ЛФ ДЗ не отмечено. Таким образом, введение ЛФ ДЗ мышам приводило к снижению выраженности фиброза, при этом механизмы фибролиза в легких и печени различались

EXPRESSION OF PROTEIN GENES PARTICIPATING IN FIBROPLASTIC PROCESSES IN MICE LUNG DURING THE DEVELOPMENT OF TUBERCULOUS INFLAMMATION

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

Соединительная ткань и проблемы ее патологических состояний

This review and discussion article focuses on the physiology and pathology of connective tissue system and its interaction with mononuclear phagocyte system (MPS) in initiation and development of fibrosis. The study presents the perspective on fibrotic conditions as hypertrophied nonspecific body reactions aimed at maintaining homeostasis and initiated by pathologic (in terms of scale and duration of manifestations) activation of MPS cells resulting from their endocytosis of biocompatible factors of different origin accompanied by nonspecific activation of expression, synthesis, and secretion of lysosomal enzymes and growth factors by MPS cells. This perspective is supported by the authors’ own findings as well as evidence published in studies of other authors. Authors’ findings support and illustrate the above conclusions using data on the modulation of functional status of macrophages and fibroblasts as well as data on prevention and correction of fibrotic processes in different experimental pathologic conditions. Статья носит обзорный дискуссионный характер, посвящена проблемам физиологии и патологии системы соединительной ткани, ее взаимодействиям с системой мононуклеарных фагоцитов (СМФ) в инициации и реализации процессов фиброзирования. Изложен и аргументрован собственными данными и результатами исследований иных авторов взгляд на фибротические состояния как на «гипертрофированную» неспецифическую реакцию организма, направленную на сохранение гомеостаза, в которой инициирующую роль играет патологическая (по масштабам и продолжительности проявлений) активация клеток СМФ как результат эндоцитоза ими биосовместимых факторов различной природы, сопряженный с неспецифической активацией экспрессии, синтеза и секреции ими лизосомальных ферментов и ростовых факторов. Приведены собственные данные, аргументирующие и иллюстрирующие эти положения результатами модуляции функционального состояния макрофагов и фибробластических клеток, профилактики и коррекции фибротических процессов при различных патологических состояниях в эксперименте.

INFLUENCE OF MACHINING ON QUALITY PARAMETERS OF OPTICAL METAL PRODUCTS

The article gives recommendations about the technological support of the given optical characteristics of metal products. The main task at providing light reflectance of surfaces is smoothing of roughnesses on a surface and providing surface cleanliness. The criterion of surface roughness and the work function of electrons have the greatest connection with the performance characteristics of optical metal products. The surface properties are determined by the double electric layer at the surface. Each subsequent stage of abrasive polishing should be carried out with a smaller grain size of an abrasive of not more than Rmax roughness, obtained in the previous stage

ROUGHNESS OF PROCESSED SURFACES UNDER ABRASIVE POLISHING

The obtained analytical dependences for determining the basic parameters of the surface roughness during abrasive polishing are presented with modeling the cutting grains in the form of a sphere and considering the ordered arrangement of grains. It is shown that with a decrease in the thickness of the cut, the ratio of the altitude parameters of the surface roughness max Ra R / increases, reaching values of 20 ... 30 and more. This is consistent with the experimental data obtained by abrasive polishing. Consequently, the modeling of abrasive grains in the form of a sphere is more in line with the actual conditions for the formation of surface roughness in both abrasive polishing and grinding. Calculations established that the process of abrasive polishing proceeds under conditions corresponding to the transition from the cutting process to the process of friction of the grain with the material being processed. It is also shown that with the reduction of the ratio max Ra R / to 4 ... 6 (corresponding to the grinding conditions), the process of metal removal and the formation of surface roughness occurs in a stable cutting process. This establishes a close relationship of the relationship max Ra R / with the ratio of the thickness of the cut and the radius of rounding of the cutting edge of the abrasive grain. It has been experimentally established that when the ball is smoothed out, the ratio max Ra R / = 14.2, and Ra = 0.1 mkm. At fine turning with a diamond tool max Ra R / = 21.2, and Ra = 0.1 micron. When abrasive polishing max Ra R / = 30, and Ra = 0.1 micron. The obtained results of theoretical and experimental studies indicate the possibility of a significant decrease in the surface roughness in abrasive polishing, which opens up new technological possibilities for its practical use

Connective tissue and the problems of its pathological conditions

This review and discussion article focuses on the physiology and pathology of connective tissue system and its interaction with mononuclear phagocyte system (MPS) in initiation and development of fibrosis. The study presents the perspective on fibrotic conditions as hypertrophied nonspecific body reactions aimed at maintaining homeostasis and initiated by pathologic (in terms of scale and duration of manifestations) activation of MPS cells resulting from their endocytosis of biocompatible factors of different origin accompanied by nonspecific activation of expression, synthesis, and secretion of lysosomal enzymes and growth factors by MPS cells. This perspective is supported by the authors’ own findings as well as evidence published in studies of other authors. Authors’ findings support and illustrate the above conclusions using data on the modulation of functional status of macrophages and fibroblasts as well as data on prevention and correction of fibrotic processes in different experimental pathologic conditions

Study of BCG Granuloma Macrophage Morphofunctional Status

We studied the morphofunctional and cytophysiological status of macrophages emigrating from BCG granulomas forming in spleen and free splenic macrophages that are not associated with granulomas. The experimental BCG granulomatosis was induced by intravenous injection of male BALB/c mice with BCG vaccine mycobacteria. The number of granulomas in spleen, their diameter, the proportion of granuloma macrophages with mycobacteria, the number of mycobacteria in granuloma macrophages, the proportion of live bacteria in granuloma macrophages and the number of granulomas macrophages capable of expressing IL-1α, TNF-α, GM-CSF were evaluated. BCG granulomas were explanted in cultures in vitro . Fractions, containing free splenic macrophages from BCG-infected animals, were explanted in separate cultures in vitro . The phagocytic activity of macrophages that migrated from BCG granulomas explanted in cultures one month after mycobacterial infection of mice, was much higher than those of splenic macrophages of intact mice. The phagocytic activity of free macrophages and macrophages from granulomas decreased with time after infection. By contrast, the antimycobacterial activity of free splenic macrophages and macrophages from BCG granulomas increased with time after infection. The correlational analysis showed that there are different correlational relationships between the number of granuloma macrophages expressing IL-1α, TNF-α, GM-CSF and phagocytic activity of macrophages from BCG granulomas. The results of the study are important for understanding the molecular and cellularmechanisms of development of chronic granulomatous inflammation induced by mycobacterial infection