ФЕНОМЕН НЕОПРЕДЕЛЕННОСТИ И ОПЫТ КОСМИЗМА В ДИСКУРСЕ ОБРАЗОВАНИЯ

The author declares, modern education is intended to be an assertion and action; and concepts of moderntimes are characterized by interest in the unrendering of religious experience, language, dictionary, mentality, which has greatly to do with education. The article provides an analysis of the interaction between uncertainty phenomenon and the ideas of cosmism in educational discourse. Uncertainty is considered as an event and reflection. This gives the opportunity to understand not only the ontological, epistemic and ethico-aesthetic aspects of uncertainty, but also to outline the prospects in the field of education, which is associated primarily with the construction of a systemic and holistic picture of education in dialogue with the ideas of cosmism. Cosmism as the thought event focuses on approving educational action. In cosmism correlated religious values and the projective thoughts, images and ideas of philosophy, natural science views, prose and poetry. The article presents semantic and categorical analysis of images and concepts that arise in topological unity of uncertainty and cosmism. Because the concept of uncertainty is invariant significant for group and personal self-actualization of social actors, a concept explored in the context of cosmism, with the utmost fulness of ideas about the Genesis of society and the individual. Ultimately, the topic of uncertainty facing the problem of overcoming of postmodern relativism and the constructive comprehension of the meanings of the generic unity of philosophy and new educational programs.Современное образование призвано быть утверждением и действием. А представления о современности характеризуются интересом к непереводимости религиозного опыта, языка, словаря, ментальности, что существенным образом связано с образованием. В статье дается анализ взаимодействия феномена неопределенности и идей космизма в дискурсе образования. Неопределенность рассмотрена как событие и рефлексия. Это дает возможность понять не только онтологические, гносеологические и этико-эстетические аспекты неопределенности, но и конструктивно наметить перспективы в области образования, что связано прежде всего с построением системной и целостной картины образования в диалоге с идеями космизма. Космизм как событие мысли ориентирован на утверждающее образовательное действие. В космизме соотнесены религиозные ценности и проективная мысль, образы и идеи философии, естественно-научные взгляды, проза и поэзия.В статье осуществлен семантический и категориальный анализ образов и понятий, возникающих в топологическом единстве неопределенности и космизма. Поскольку концепт неопределенности инвариантно значим для группового и личностного самоосуществления социальных субъектов, концепт исследован в контексте космизма, обладающего предельной полнотой представлений о бытии общества и личности. В конечном счете тема неопределенности обращена к проблематике преодоления постмодернистского релятивизма и осмыслению конструктивных смыслов родового единства философии и образовательных программ современности

Evolution of climate, glaciation and subglacial environments of Antarctica from the deep ice core and Lake Vostok water sample studies (Key results of implementation of the Russian Science Foundation project, 2014–2016)

Work on the project focused on the following five areas: 1)  field works in Antarctica at Vostok and Concordia stations; 2)  experimental and theoretical studies in the field of ice core and paleoclimate research; 3) experimental and theoretical works related to the exploration of subglacial Lake Vostok; 4) development of technology and drilling equipment for deep ice coring and exploration of subglacial lakes; 5) upgrading the analytical instrumentation in the Climate and Environmental Research Laboratory (CERL) of the Arctic and Antarctic Research Institute. The main achievements in the field of ice core and paleoclimate research include 1) further elaboration of a new method of ice core dating, which is based on the link between air content of ice and local insolation, 2) investigation of the possible applications of the 17O-excess measurements in ice core to the paleoclimate research, 3)  a better understanding of the mechanisms of the formation of relief-related variations in the isotopic content of an ice core drilled in the area of Antarctic megadunes, and 4) obtaining the first reliable data set on the variations of the 17O-excess in the Vostok core corresponding to marine isotope stage 11. As part of our studies of subglacial Lake Vostok, we have obtained a large body of new experimental data from the new ice core recovered from the 5G-3 borehole to the surface of the subglacial lake. Stacked profiles of isotopic composition, gas content and the size and orientation of the ice crystals in the lake ice have been composed from the data of three replicate cores from boreholes 5G-1, 5G-2 and 5G-3. The study reveals that the concentration of gases in the lake water beneath Vostok is unexpectedly low. A clear signature of the melt water in the surface layer of the lake, which is subject to refreezing on the icy ceiling of Lake Vostok, has been discerned in the three different properties of the accreted ice (the ice texture, the isotopic and gas content of the ice). These sets of data indicate in concert that poor mixing of the melt (and hydrothermal) water with the resident lake water and pronounced spatial and/or temporal variability of local hydrological conditions are likely to be the characteristics of the southern end of the lake. A considerable part of the funding allocated by the RSF to this project was used for upgrading the analytical instrumentation for ice core studies in the CERL of AARI. Using this grant, we purchased and started working with the Picarro L-2140i, a new-generation laser mass analyzer, and set the upgraded mass spectrometer Delta V Plus into operation. The new equipment was used to carry out research planned as part of the project, including the setting up and carrying out of new measurements of 17О in ice cores

Postoperative cognitive dysfunction: etiology, clinical features, diagnosis

Introduction. The present study analyzed the possibility of using neuropsychological tests to assess postoperative cognitive dysfunction. New data were obtained: in the postoperative period, hippocampal memory impairments predominate in patients, which makes it expedient to use methods for diagnosing primary modal-nonspecific memory disorders in patients who are to undergo neurosurgical intervention on the spinal cord.The aim of the study to evaluate the influence of surgery with anesthesia on the cognitive functions of middle-age patients.Materials and methods. The study included 20 middle-aged patients. All patients had to undergo spinal surgery. Patients received total intravenous anesthesia with propofol induction (4–12 mg/kg/hr). Cognitive functions before and after the operation were made with the use of the MoCA, TMT A and B, FCSRT, state-trait anxiety inventory test (STAI).Results. The development of POCD was noted in 15% of cases. The patients showed a decrease in the FCSRT prompt index (1st day = 87 ± 9.0; 2nd day = 83 ± 15; p = 0,0005), while the overall severity of cognitive impairments (total score of MoCA) did not change significantly (standard deviation according to MoCA: 24.25 ± 2.86 on day 1 and 24 ± 3.24 on the second day, p = 0.61). The RT level decreased by day 2: 44.65 ± 7.4 versus 41.1 ± 8.2 (p = 0.001). Correlation analysis did not show the relationship between the age of patients, education level, comorbidity and development of POCD; however, the duration of anesthesia was associated with a decrease in MoCA scores (Pearson’s correlation coefficient r = –0.44; p = 0.050).Conclusion. Thus, our study shows that the study of hippocampal memory impairments is important in patients with POCD. These data differ from the data of researchers presented earlier, where the most important clinical manifestations of POCD are considered to be a decrease in attention and speed of mental processes. Of course, the small sample size dictates the need for additional research

Evaluation of the effectiveness of the analgesic effect of selective and non-selective cyclooxygenase blockers in the composition of multimodal analgesia after knee joint endoprosthesis replacement

The purpose of the work is to compare the effectiveness of anesthesia with the use of a highly specific blocker COX-2 and a dedicated cyclo-oxygenase blocker COX-1 and COX-2 lornoxicam as part of multimodal analgesia in patients after primary knee replacement. The material was the cases of knee prosthesis (N=196) using multimodal analgesia; patients were divided into two groups, depending on the type of anesthesia, in accordance with the developed scheme of pharmacotherapy: I – receiving celecoxib (n=98) and II - lornoxicam (n=98). Methods for evaluating the effectiveness of anesthesia were the visual analogue scale (VAS), the KSS knee joint function evaluation scale before surgery and on the 5th day after it; analysis of the features of early verticalization, the patient's need for additional pain relief after surgery; costs of drug therapy are calculated. Results. Patients of both groups were comparable in age and average duration of hospitalization. The pain syndrome assessment on the VAS scale showed a higher efficacy of pain relief on days 1 and 5 in group II (4.1 ± 0.1 versus 3.5 ± 0.1 and 1.9 ± 0.04 versus 1.6 ± 0.1 points respectively) (p≤0.05). Evaluation of the functional activity of the prosthetic knee joint on the KSS scale did not reveal any differences between the groups. Of the features of early verticalization on the first day after surgery, a higher percentage of weakness in the legs (79.6%) and nausea (70.4%) was noted in group I, and a higher percentage of dizziness (15.3%) and hemodynamic disorders (6.1% of cases). The cost of providing basic pain therapy in group I was 2.4 times higher than in group II, with the same costs for additional anesthesia with solutions of paracetamol and narcotic analgesics. Conclusions. As part of multimodal analgesia, Lornoxicam showed a higher efficacy in relieving pain syndrome at a low cost of a course of treatment compared with celecoxib.Цель работы - сравнение эффективности обезболивания при использовании высокоспецифичного блокатора ЦОГ-2 целекоксиба и неспецифичного блокатора циклооксигеназы ЦОГ-1 и ЦОГ-2 лорноксикама в составе мультимодальной анальгезии у пациентов после первичного эндопротезирования коленного сустава. Материалом послужили случаи протезирования коленных суставов (N=196) с использованием мультимодальной анальгезии; в зависимости от типа обезболивания, в соответствии с разработанной схемой фармакотерапии, пациенты разделены на две группы: I - получающие целекоксиб (n=98) и II - лорноксикам (n=98). Методами оценки эффективности обезболивания являлись визуально-аналоговая шкала (ВАШ), шкала оценки функции коленного сустава KSS до операции и на 5 сутки после неё; анализ особенностей ранней вертикализации, потребности пациента в дополнительном обезболивании после операции; рассчитаны затраты на медикаментозную терапию. результаты. Пациенты обеих групп были сопоставимы по возрасту и средней длительности госпитализации. оценка болевого синдрома по шкале ВАШ показала более высокую эффективность купирования болевого синдрома на 1 и 5 сутки во II группе (4,1±0,1 против 3,5±0,1 и 1,9±0,04 против 1,6±0,1 балла соответственно) (p≤0,05). оценка функциональной активности протезированного коленного сустава по шкале KSS не выявила различий между группами. особенности ранней вертикализации в 1 сутки после операции: в I группе - более высокий процент слабости в ногах (79,6%) и тошноты (70,4%), во II - выше процент головокружения (15,3%) и нарушений гемодинамики (6,1% случаев). Затраты на обеспечение базовой обезболивающей терапии в I группе в 2,4 раза превысили показатель II группы, при равных затратах на дополнительное обезболивание растворами парацетамола и наркотических анальгетиков. Выводы. Лорноксикам в составе мультимодальной анальгезии показал более высокую эффективность купирования болевого синдрома при низкой стоимости курсового лечения по сравнению с целекоксибом

Diagnostically significant differences septic and aseptic instability of endoprosthesis components during arthroplasty of large joints

The purpose of the work is to analyze the results of laboratory, microbiological and instrumental studies to search for screening criteria for the difference between aseptic and septic instability of endoprosthesis components after knee and hip joint arthroplasty. The materials contained 146 cases of revision arthroplasty of the knee and hip joints, performed under the conditions of Federal State Budgetary Institution Federal Center of Traumatology, Orthopedics and endoprosthesis replacement of Ministry of Health of the Russian Federation (Cheboksary) for a 3-year period, including cases of aseptic instability - 69, septic instability-77. By methods for laboratory diagnosis were used to evaluate the blood levels of leukocytes, stab neutrophils, ESR, C-reactive protein (CRP), presepsin, procalcitonin, D-dimer, interleukin-6. Using ultrasound (ultrasonic) examination of the periprosthetic zone, the presence of fluid, granulation tissue in the joint cavity, altered lymph nodes was determined. Before the operation, the level of cytosis and cellular composition were determined in the synovial fluid; tissue bioptates, removed components of implants (after ULTRASONIC treatment) with sowing on the microflora were studied intraoperatively. Intraoperative tissue biopsies were used to make smears-prints on the glass, with gram staining, estimating the number of leukocytes and neutrophils in the field of vision. Results. Determination of indicators of ESR, presepsin and interleukin-6, the level of which goes beyond the generally recognized normal values in the presence of infection, can be recommended as a screening test in the diagnosis of the infectious nature of instability of the components of the endoprosthesis of large joints. The second stage of differential diagnosis of septic and aseptic instability can be the detection of lymphadenopathy. The third (final) stage of determining the infectious nature of instability is an invasive technique to determine the level of cytosis with the calculation of neutrophils in the synovial fluid.Цель работы - анализ результатов лабораторных, микробиологических и инструментальных исследований для поиска скрининг-критериев отличия асептической и септической нестабильности компонентов эндопротеза после артропластики коленных и тазобедренных суставов. Материалами послужили 146 случаев ревизионной артропластики коленных и тазобедренных суставов, выполненной в условиях Федерального государственного бюджетного учреждения «Федеральный центр травматологии, ортопедии и эндопротезирования» Министерства здравоохранения российской Федерации (г. Чебоксары) за 3-летний период, из них случаев асептической нестабильности - 69, септической нестабильности - 77. Методами лабораторной диагностики проводилась оценка содержания в крови лейкоцитов, палочкоядерных нейтрофилов, СОЭ, С-реактивного белка (СРБ), пресепсина, прокальцитонина, Д-димера, интерлейкина-6. С помощью ультразвукового (УЗ) исследования перипротезной зоны определяли наличие жидкости, грануляционной ткани в полости сустава, измененных лимфатических узлов. до операции в синовиальной жидкости определяли уровень цитоза и клеточный состав; интраоперационно исследовались тканевые биоптаты, удаленные компоненты имплантов (после УЗ обработки) с посевом на микрофлору. Из интраоперационных тканевых биоптатов делали мазки-отпечатки на стекле, с окрашиванием по Граму, оценивая количество лейкоцитов и нейтрофилов в поле зрения. результаты. Определение показателей СОЭ, пресепсина и интерлейкина-6, уровень которых выходит за пределы общепризнанных нормальных значений при наличии инфекции, может быть рекомендовано в качестве скрининг-теста при диагностике инфекционной природы нестабильности компонентов эндопротеза крупных суставов. Вторым этапом дифференциальной диагностики септической и асептической нестабильности может служить выявление лимфоаденопатии. третьим (заключительным) этапом определения инфекционной природы нестабильности является инвазивная методика с определением уровня цитоза с подсчетом нейтрофилов в синовиальной жидкости

Novel allosteric mechanism of p53 activation by small molecules for targeted anticancer therapy

Given the immense significance of p53 restoration for anti-cancer therapy and that p53-activating molecules are in clinical trials, elucidation of the mechanisms of action of p53-activating molecules is of the utmost importance. Here we report a discovery of a novel allosteric modulation of p53 by small molecules, which is an unexpected turn in the p53 story. We identified a structural element involved in allosteric regulation of p53, whose targeting by small molecules RITA, PpIX and licofelone blocks the binding of two p53 inhibitors, MDM2 and MDMX, thereby restoring p53 function. Deletion and mutation analysis followed by molecular modeling and its thorough validation, identified the key p53 residues S33 and S37 targeted by RITA and PpIX. We propose that the binding of small molecules to the identified site in p53 induces a conformational trap preventing p53 from the interaction with MDM2 and MDMX. These results point to a high potential of allosteric activators as targeted drugs. Our study provides a basis for the development of therapeutics with a novel mechanism of action, thus extending the p53 pharmacopeia

Эволюция климата, оледенения и подледниковой среды Антарктиды по данным исследований ледяных кернов и проб воды озера Восток (Основные итоги работ по проекту РНФ, 2014–2016 гг.)

Work on the project focused on the following five areas: 1)  field works in Antarctica at Vostok and Concordia stations; 2)  experimental and theoretical studies in the field of ice core and paleoclimate research; 3) experimental and theoretical works related to the exploration of subglacial Lake Vostok; 4) development of technology and drilling equipment for deep ice coring and exploration of subglacial lakes; 5) upgrading the analytical instrumentation in the Climate and Environmental Research Laboratory (CERL) of the Arctic and Antarctic Research Institute. The main achievements in the field of ice core and paleoclimate research include 1) further elaboration of a new method of ice core dating, which is based on the link between air content of ice and local insolation, 2) investigation of the possible applications of the 17O-excess measurements in ice core to the paleoclimate research, 3)  a better understanding of the mechanisms of the formation of relief-related variations in the isotopic content of an ice core drilled in the area of Antarctic megadunes, and 4) obtaining the first reliable data set on the variations of the 17O-excess in the Vostok core corresponding to marine isotope stage 11. As part of our studies of subglacial Lake Vostok, we have obtained a large body of new experimental data from the new ice core recovered from the 5G-3 borehole to the surface of the subglacial lake. Stacked profiles of isotopic composition, gas content and the size and orientation of the ice crystals in the lake ice have been composed from the data of three replicate cores from boreholes 5G-1, 5G-2 and 5G-3. The study reveals that the concentration of gases in the lake water beneath Vostok is unexpectedly low. A clear signature of the melt water in the surface layer of the lake, which is subject to refreezing on the icy ceiling of Lake Vostok, has been discerned in the three different properties of the accreted ice (the ice texture, the isotopic and gas content of the ice). These sets of data indicate in concert that poor mixing of the melt (and hydrothermal) water with the resident lake water and pronounced spatial and/or temporal variability of local hydrological conditions are likely to be the characteristics of the southern end of the lake. A considerable part of the funding allocated by the RSF to this project was used for upgrading the analytical instrumentation for ice core studies in the CERL of AARI. Using this grant, we purchased and started working with the Picarro L-2140i, a new-generation laser mass analyzer, and set the upgraded mass spectrometer Delta V Plus into operation. The new equipment was used to carry out research planned as part of the project, including the setting up and carrying out of new measurements of 17О in ice cores.Изложены основные результаты работ, выполненных Лабораторией изменений климата и окружающей среды ААНИИ по проекту Российского научного фонда в 2014–2016 гг. Показано, что поддержка фонда способствовала получению научных результатов международного уровня в двух приоритетных направлениях антарктических исследований  – реконструкции палеоклимата по ледяным кернам и изучении подледниковой среды Антарктиды

Rapid selection of BRCA1-proficient tumor cells during neoadjuvant therapy for ovarian cancer in BRCA1 mutation carriers

Ovarian carcinomas (OC) often demonstrate rapid tumor shrinkage upon neoadjuvant chemotherapy (NACT). However, complete pathologic responses are very rare and the mechanisms underlying the emergence of residual tumor disease remain elusive. We hypothesized that the change of somatic BRCA1 status may contribute to this process. The loss-of-heterozygosity (LOH) at the BRCA1 locus was determined for 23 paired tumor samples obtained from BRCA1 germ-line mutation carriers before and after NACT. We observed a somatic loss of the wild-type BRCAI allele in 74% (17/23) of OCs before NACT. However, a retention of the wild-type BRCA1 copy resulting in a reversion of LOH status was detected in 65% (11/17) of those patients after NACT. Furthermore, we tested 3 of these reversion samples for LOH at intragenic BRCA1single nucleotide polymorphisms (SNPs) and confirmed a complete restoration of the SNP heterozygosity in all instances. The neoadjuvant chemotherapy for BRCA1-associated OC is accompanied by a rapid expansion of pre-existing BRCA1-proficient tumor clones suggesting that continuation of the same therapy after NACT and surgery may not be justified even in patients initially experiencing a rapid tumor regression. (C) 2017 Elsevier B.V. All rights reserved.Peer reviewe

Пространственная изменчивость изотопного состава и скорости накопления снега на снегомерном полигоне станции Восток (Центральная Антарктида)

The knowledge of the spatial distribution of the snow accumulation rate and isotopic composition in different scales, from local to continental, over the Antarctic Ice Sheet is critically important for the interpretation of the paleoclimate data obtained from deep ice cores, for correct assessment of the ice sheet mass balance, etc. With this in mind, we have synthesized geodetic, glaciological and geochemical data collected in the vicinity of central Antarctic Vostok station in 1970–2017 in order to shed light on the processes governing the spatial distribution of snow isotopic composition and accumulation rate in the spatial scale from 100 to 1000 m. First, we have discovered that snow surface height and snow accumulation rate field are strongly affected by the influence of the logistic convoy route annually operating between Russian Antarctic stations Vostok and Progress. This influence is detectable up to 1 km leeward from the route. At the same time the isotopic composition of the upper 10 cm of the snow does not show any anomalies in the vicinity of the route. This is an unexpected result, because large anomalies of the ice sheet surface (e.g., megadunes) are known to affect the snow isotopic composition. Second, in the undisturbed part of the snow surface near Vostok station we have discovered quasi-periodic (with the wavelength of about 400 m) low-amplitude variations of the surface height that are covariant with the corresponding waves in snow accumulation and isotopic composition. We suggest that spatial variability of the snow isotopic composition is due to the different ratio of summer and winter precipitation deposited in different locations, as evident from a strong negative correlation between δD and dxs parameters. The results of this study may explain the nature of the low-frequency noise (with the time-scale from decades to centuries) observed in the climate records obtained from shallow and deep ice cores in central Antarctica.Изучение пространственного распределения скорости накопления и изотопного состава снега в различных масштабах на поверхности антарктического ледяного покрова критически важно для интерпретации палеоклиматических данных по глубоким ледяным кернам, для корректной оценки баланса массы ледяного щита и т.д. Впервые на основании большого объема геодезических, гляциологических и геохимических данных была детально изучена пространственная изменчивость изотопного состава и скорости накопления снега в районе станции Восток (Центральная Антарктида) в пространственном масштабе от 100 до 1000 м. Показано, что высота снежной поверхности и скорость накопления снега изученной территории существенно преобразованы влиянием проходящей здесь трассы санно-гусеничных походов между станциями Восток и Прогресс. В ненарушенной части данной территории выявлены квазипериодические колебания высоты поверхности с горизонтальными размерами порядка 400 м («мезодюны») и ассоциированные с ними аномалии изотопного состава и скорости накопления снега. Полученные результаты могут прояснить природу низкочастотного шума, наблюдаемого в климатических рядах, полученных по антарктическим ледяным кернам

Противовоспалительный и регенеративный эффект подавления гипоксийного сигналинга на модели хронической обструктивной болезни легких

The aim of this study was to investigate anti-inflammatory and regenerative effects of inhibited activation of hypoxic signaling in COPD model using cyclooxygenase-2 (COX-2)-dependent pro-inflammatory cascade inhibition. Methods. COPD was modelled in rats by nitrogen dioxide (NO2, 30-40 mg×m–3) exposure for 90 days. Celecoxib was used as COX-2 inhibitor. The study group rats were given celecoxib (25 mg×kg–1) through an esophageal probe after 30 days of exposure. Control rats were given saline solution. The group 3 rats were intact. The rats were put out of the experience using cervical dislocation after 60 and 90 days of NO2 exposure. Bronchoalveolar lavage fluid (BALF) cytology was analyzed. COX-2, hypoxia-inducible factor-1α (HIF-1α), interleukin-17 (IL-17), and surfactant protein D (SP-D) were measured in BALF using ELISA method. Histological examination of the lung tissue was also performed. Results. 90-day exposure of NO2 resulted in 7.7-fold increase in BALF neutrophil count compared to that in intact rats. Pro-inflammatory mediators (СOX-2, HIF-1α, and IL-17) significantly increased and SP-D level decreased in BALF. Administration of celecoxib was accompanied by normalization of BALF cytology profile and decrease in COX-2, HIF-1α, and IL-17 levels in BALF; this could indicate a reduction in the hypoxic signaling activity and in inflammation. The growth of SP-D concentration could be considered as a result of the alveolar epithelium restoration. This was confirmed by histological examination of the lung tissue. Conclusion. COX-2 inhibition suppressed HIF-1α-signaling and decreased the lung inflammation. The results confirm a functional and regulatory relationship between HIF-1α and COX-2 signaling cascades that could be a therapeutic target for preventing the progression of inflammation and airway remodeling in COPD.Цель. Оценка противовоспалительного и регенеративного эффекта предотвращения активации гипоксийного сигналинга на модели хронической обструктивной болезни легких (ХОБЛ) путем ингибирования циклооксигеназы-2 (СОХ-2)-зависимого провоспалительного каскада. Материалы и методы. При помощи экспозиций диоксидом азота (NO2, 30–40 мг / м3) в течение 90 дней у крыс создана модель ХОБЛ. В качестве ингибитора СОХ-2 применялся целекоксиб. С 30-го дня крысам 1-й группы через пищеводный зонд вводился целекоксиб (25 мг / кг); животные 2-й группы (контроль) получали 0,9%-ный NaCl. Интактные крысы составили 3-ю группу. Животные выводились из опыта после 60 и 90 дней экспозиции NO2 путем цервикальной дислокации. При этом выполнялась цитография бронхоальвеолярной лаважной жидкости (БАЛЖ), определялось содержание COX-2, гипоксия-индуцибельного фактора-1a (HIF-1a), интерлейкина (IL)-17, сурфактантного протеина D (SP-D) методом ELISA. Выполнено гистологическое исследование легочной ткани. Результаты. Показано, что после 90-дневной экспозиции NO2 в БАЛЖ контрольных особей содержание нейтрофилов в 7,7 раза превышало интактное значение. Достоверно возрастало содержание провоспалительных медиаторов СОХ-2, HIF-1α, IL-17, а уровень SP-D снижался. Применение целекоксиба сопровождалось нормализацией цитологического профиля БАЛЖ и уменьшением содержания СОХ-2, HIF-1α, IL-17, что свидетельствовало о снижении активности гипоксийного сигналинга и воспалительного процесса. Значительно возрастала концентрация SP-D, что можно рассматривать как следствие восстановления морфологической структуры бронхоальвеолярного эпителия, о чем свидетельствовали данные гистологического исследования легочной ткани. Заключение. При ингибировании СОХ-2 отмечен супрессивный эффект на HIF-1α-сигналинг и уменьшение легочного воспаления. Полученные результаты подтверждают функционально-регуляторную связь HIF-1α и СОХ-2-сигнальных каскадов, которая может быть терапевтической мишенью для предотвращения прогрессирования воспаления и ремоделирования дыхательных путей при ХОБЛ