Purpose: The aim of our research was to study sex differences and the severity of inflammatory changes in target organs and the peculiarities of immunological disorders when low and high doses of lipopolysaccharide (LPS) were administered to rats. Methods: Male and female 2- to 3-month-old Wistar rats (200–250 g) were injected intraperitoneally with Escherichia coli LPS in one of two doses: 1.5 or 15 mg/kg. In a day after the LPS injection, we studied endotoxin, corticosterone, sex steroids, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) activity levels in the serum; morphological disorders in the lung, liver, thymus, and spleen; ex vivo production of IL-2, IL-4, tumor necrosis factor (TNF), and interferon γ (IFNγ) by splenic cells activated by ConA; and relative amount of T- and B-lymphocytes in the peripheral blood. Results: After the injection of low-dose LPS, the serum endotoxin level increased only in males and was combined with a more pronounced inflammatory response in the lungs and thymus and an increase in ALT and AST activity levels without any changes in corticosterone level. After the injection of high-dose LPS, the inflammatory and pathological changes in the target organs manifested as severe endotoxemia and sex differences of pathological changes in the lungs and liver were not revealed. The level of production of IL-2, IL-4, IFNγ, and TNF by splenic cells and the number of T-lymphocytes, including cytotoxic cells, in the peripheral blood, decreased in males, which is an evidence of a pronounced suppression of the immune response. Conclusion: We have shown that the morphofunctional changes in the organs of the immune system in females and males, as well as the intensity of the sex differences of inflammation, depend on the severity of systemic inflammatory response, induced by different doses of LPS.

Medical article медицинская статья

Introduction. Data about the role of components of adipose tissue in the repair of damaged uterine walls are limited, although a number of authors claim that cell-based drugs from adipose tissue have a positive effect on the repair of damaged uterine walls in laboratory rodents. Meanwhile, stem cells derived from adipose tissue are considered to be the most promising type of cells in regenerative medicine. The aim of the studywas to evaluate the adipocyte components in the uterine wall of rats in healing after a full-thickness surgi-cal incision. Materials and methods. We conducted the study on 40 female Sprague Dawley rats. The animals were sub-jected to a full-thickness longitudinal incision in the wall of the right uterine horn, with the left one serving as an intact control. We carried out morphological examinations of the uterine walls daily in 5 animals from day 1 to 7 and on day 15. The sections from paraffin blocks were stained with hematoxylin and eosin and Mallory’s trichrome staining. Immunohistochemistry detected FABP4+ adipocytes and CD68+ macrophages. The morphometric study was carried out using the Leica system (Leica, Germany). The results underwent processing in the Statistica 12 software (StatSoft). Results. We noticed the period of the most active interaction of adipose tissue with the damaged horn to last from day 3 to 15 and coincide with the macrophage activation in the healing zone. The intact left uterine horn was not involved in the interaction processes with the mesenteric adipose tissue. Starting from day 3 FABP4+ cells in the uterine wall of the operated horn formed groups, creating rounded nest-like structures. Clusters of FABP4+ cells were localized in the healing zone, near the suture material, and in the perime-trium near the mesentery attachment sites. The changes over time of the indicators of the area of cell nests depended on the localization and duration of healing. There were no FABP4+ cells in the left intact horn. Conclusion. We characterized the morphological interaction of adipose tissue with the damaged uterine wall during the first two weeks after a full-thickness surgical incision of the rat uterine horn. The results of the study indicate that adipocytes take an active part in the healing after a surgical incision of the rat uterine wall at the earliest stages. Keywords: rat uterus, hysterotomy, healing, adipocytes, macrophages

(1) Background: The components of the fibrinolytic system and its main component, plasminogen, play a key role in the first months of pregnancy. The effect of autoantibodies interacting with plasminogen in the formation of retrochorial hematoma is unknown. The aim of our study was to determine the role of plasminogen and IgA, IgM, and IgG, which bind to plasminogen, in retrochorial hematoma. (2) Methods: Prothrombin time (PT), thrombin time (TT), partial activated thromboplastin time (aPTT), soluble fibrin-monomer complex (SFMC), D-dimer, plasminogen activity (%Plg), plasminogen concentration (Plg), and the levels of IgG (IgG-Plg), IgM (IgM-Plg), IgA (IgA-Plg) interacting with plasminogen were determined in plasma samples of 57 women with normal pregnancy and 16 with retrochorial hematoma. (3) Results: %Plg in plasma samples from women with retrochorial hematoma was significantly lower than in plasma samples from women with normal pregnancy. The diagnostic significance of %Plg in the ROC analysis was AUC = 0.85. A direct correlation was found between aPTT and the level of autologous IgM interacting with plasminogen. (4) Conclusions: A decrease in the activity of plasminogen in the blood serum of women in the first trimester of pregnancy may indicate disturbances in the hemostasis system and the formation of retrochorial hematoma. According to the results of the study, it is possible to recommend the determination of plasminogen activity in the management of pregnant women in gynecological practice.

Преэклампсия (ПЭ) — специфичное для беременности мультисистемное воспалительное заболевание, характеризующееся развитием de novo артериальной гипертензии и протеинурии, а также полиорганной дисфункцией, представляющее угрозу для матери и плода. Патогенез ПЭ связан с системными дисфункциональными изменениями эндотелия сосудов и избыточной воспалительной реакцией матери, частично опосредованной освобождением плацентарного дебриса в материнскую циркуляцию, уровень депортации которого повышен при ПЭ. Кроме того, нарушение процессов ангиогенеза, инвазии трофобласта и ремоделирования спиральных артерий матки идентифицировано как ключевой фактор патогенеза ПЭ. Появляется все больше информации о возможном вовлечении в патогенез ПЭ нейтрофилов (НФ), которые в процессе активации формируют и высвобождают в межклеточное пространство нейтрофильные внеклеточные ловушки (neutrophil extracellular traps, NETs), предназначенные, главным образом, для элиминации патогенных микроорганизмов. Однако определенные условия, такие как конститутивная активация НФ, нарушение супрессорных механизмов и избыточная продукция NETs могут вносить вклад в патофизиологию ПЭ. Наряду с этим активированные НФ, по-видимому, играют важную роль как в усилении воспалительного ответа, так и в нарушении процесса свертывания крови и повышении риска тромбообразования. В настоящем обзоре представлены современные данные о биологиии NETs, механизме их формирования в зависимости от стимулов микроокружения, а также о потенциальной роли NETs в патогенезе ПЭ.