mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-BPI-2090mimmun-2090Research ArticleОБЗОРЫREVIEWSТромбоциты в развитии сепсиса, септического шока и синдрома полиорганной недостаточностиBlood platelets in the development of sepsis, septic shock and multiple organ failure syndromehttps://orcid.org/0000-0002-2418-9368СеребрянаяН. Б.SerebryanayaN. B.

Серебряная Наталья Борисовна – доктор медицинских наук, профессор, заведующая лабораторией общей иммунологии отдела иммунологии

197376, Санкт-Петербург, ул. Акад. Павлова, 12

Serebryanaya Natalya B., PhD, MD (Medicine), Professor, Head, Laboratory of General Immunology, Immunology Department, Institute of Experimental Medicine

197376, St. Petersburg, Acad. Pavlov str., 12

nbvma@mail.ruhttps://orcid.org/0000-0002-1412-1095ЯкуцениП. П.YakutseniP. P.

Якуцени Павел Павлович – доктор биологических наук, главный научный сотрудник Центра перспективных исследований

Санкт-Петербург

Yakutseni Pavel P., PhD, MD (Biology), Chief Research Associate, Center for Advanced Studies, Peter the Great

St. Petersburg

ypp@mail.ruФГБНУ «Институт экспериментальной медицины»РоссияInstitute of Experimental MedicineRussian FederationФГАОУ ВО «Санкт-Петербургский политехнический университет Петра Великого»РоссияPeter the Great St. Petersburg Polytechnic UniversityRussian Federation20203112202022610851096Copyright © Серебряная Н.Б., Якуцени П.П., 20212021Серебряная Н.Б., Якуцени П.П.Serebryanaya N.B., Yakutseni P.P.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.mimmun.ru/mimmun/article/view/2090

Участие тромбоцитов в развитии сепсиса наглядно иллюстрируют гемокоагуляционные нарушения и часто регистрируемая тромбоцитопения. У больных сепсисом тромбоцитопения развивается быстро, минимальные количества пластинок регистрируются на четвертый день наблюдения, после чего количество тромбоцитов обычно повышается. Длительно регистрируемая тромбоцитопения и отсутствие относительного прироста тромбоцитов определены как предикторы смерти больных. Механизмы развития тромбоцитопении при сепсисе очень разнообразны, но преобладающими являются периферические процессы, так называемое «потребление тромбоцитов», определяемое их активацией, хемотаксисом и изоляцией в микроциркуляторном русле. Недавно выявлен механизм ускоренного удаления из циркуляции тромбоцитов с десиалированнными поверхностными гликопротеинами. Сиалидазы, также известные как нейраминидазы, широко представлены у вирусов и бактерий, причем фармакологическая ингибиция сиалидаз способна противостоять тромбоцитопении при инфекционном процессе. Выявлена ключевая роль тромбоцитов в развитии септического шока. Секвестрация тромбоцитов в микрососудах легких и мозга (которая проявляется как тромбоцитопения) сопровождается быстрым выделением серотонина, который и обеспечивает развитие основных клинических проявления, таких как снижения АД, ЧСС и увеличение проницаемости капилляров. Для противодействия резкому выбросу этого медиатора предпринимаются попытки фармакологически ингибировать транспортер SERT селективными ингибиторами обратного захвата серотонина. Тромбоциты являются ключевыми участниками патогенеза таких проявления синдрома полиорганной недостаточности, как острое почечное повреждение, острый респираторный дистресс-синдром, дисфункция миокарда и сепсис-ассоциированная энцефалопатия. Для восстановления нарушенной сосудистой проницаемости при этих состояниях, особенно сепсис-ассоциированной энцефалопатии, исследуется фармакологический миметик рецепторов S1P. В обзоре обозначены возможные патогенетически значимые мишени, которые могут быть использованы для фармакологической коррекции состояний, связанных с сепсисом и сопутствующей тромбоцитопенией.

Participation of blood platelets in the development of sepsis is clearly illustrated by hemocoagulation disorders and frequently observed thrombocytopenia. In the patients with sepsis, thrombocytopenia develops rapidly, with minimal platelet counts registered on the fourth day of observation, after which the platelet counts usually rise. Continuous thrombocytopenia and absence of a relative increase in platelets are considered predictors of patient death. The mechanisms of thrombocytopenia developing in sepsis are quite diverse, but the processes in periphery are prevailing, e.g., the so-called “platelet consumption” which is determined by their activation, chemotaxis and isolation in the microvasculature. Recently, a mechanism has been identified for the accelerated removal of platelets with desialized surface glycoproteins from the circulation. Sialidases, also known as neuraminidases, are widely present in viruses and bacteria, and pharmacological inhibition of sialidases is able to withstand thrombocytopenia in the infectious process. The key role of platelets in the development of septic shock was revealed. Sequestration of platelets in the microvessels of the lungs and brain (manifesting as thrombocytopenia) is accompanied by rapid serotonin release, thus underlying the main clinical manifestations, e.g., decreased blood pressure, heart rate and increased capillary permeability. To counteract sharp release of this mediator, pharmacological attempts are made to inhibit the SERT transporter by means of selective serotonin reuptake inhibitors. Blood platelets are key participants in the pathogenesis of multiple organ failure syndromes, such as acute renal damage, acute respiratory distress syndrome, myocardial dysfunction, and sepsis-associated encephalopathy. To restore impaired vascular permeability in these conditions, in particular, sepsis-associated encephalopathy, a pharmacological S1P receptor mimetic is under study. The review specifies possible pathogenetically significant targets that can be used to perform pharmacological correction of conditions associated with sepsis and concomitant thrombocytopenia.

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