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<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">rmt</journal-id><journal-title-group><journal-title xml:lang="ru">Общая реаниматология</journal-title><trans-title-group xml:lang="en"><trans-title>General Reanimatology</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">1813-9779</issn><issn pub-type="epub">2411-7110</issn><publisher><publisher-name>FSBI "SRIGR" RAMS</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.15360/1813-9779-2018-2-60-68</article-id><article-id custom-type="elpub" pub-id-type="custom">rmt-1680</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>ЭКСПЕРИМЕНТАЛЬНЫЕ ИССЛЕДОВАНИЯ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>EXPERIMENTAL STUDIES</subject></subj-group></article-categories><title-group><article-title>Синтетический аналог лей-энкефалина предотвращает развитие эндотелиальной дисфункции in vitro</article-title><trans-title-group xml:lang="en"><trans-title>Synthetic Analogue of Leu-Enkephalin Prevents Endothelial Dysfunction in vitro</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Гребенчиков</surname><given-names>О. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Grebenchikov</surname><given-names>O. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>129110, г. Москва, ул. Щепкина, д.61/2;</p><p>107031, г. Москва, ул. Петровка, 25, стр. 2</p></bio><bio xml:lang="en"><p>61/2 Shchepkin Str., 129110 Moscow;</p><p>25 Petrovka Str., Build. 2, 107031 Moscow</p></bio><email xlink:type="simple">oleg.grebenchikov@yandex.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Овезов</surname><given-names>А. М.</given-names></name><name name-style="western" xml:lang="en"><surname>Ovezov</surname><given-names>A. M.</given-names></name></name-alternatives><bio xml:lang="ru"><p>129110, г. Москва, ул. Щепкина, д.61/2</p></bio><bio xml:lang="en"><p>61/2 Shchepkin Str., 129110 Moscow</p></bio><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Скрипкин</surname><given-names>Ю. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Skripkin</surname><given-names>Yu. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>129110, г. Москва, ул. Щепкина, д.61/2</p></bio><bio xml:lang="en"><p>61/2 Shchepkin Str., 129110 Moscow</p></bio><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Забелина</surname><given-names>Т. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Zabelina</surname><given-names>T. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>129110, г. Москва, ул. Щепкина, д.61/2</p></bio><bio xml:lang="en"><p>61/2 Shchepkin Str., 129110 Moscow</p></bio><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Улиткина</surname><given-names>О. Н.</given-names></name><name name-style="western" xml:lang="en"><surname>Ulitkina</surname><given-names>O. N.</given-names></name></name-alternatives><bio xml:lang="ru"><p>129110, г. Москва, ул. Щепкина, д.61/2</p></bio><bio xml:lang="en"><p>61/2 Shchepkin Str., 129110 Moscow</p></bio><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Луговой</surname><given-names>А. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Lugovoy</surname><given-names>A. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>129110, г. Москва, ул. Щепкина, д.61/2</p></bio><bio xml:lang="en"><p>61/2 Shchepkin Str., 129110 Moscow</p></bio><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Приходько</surname><given-names>А. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Prikhodko</surname><given-names>A. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>119992, г. Москва, ул. Ленинские Горы, д.1 стр.40;</p><p>119992, г. Москва, ул. Ленинские Горы, дом 1 стр. 73А</p></bio><bio xml:lang="en"><p>1 Leninskie Gori Str., Build. 40, Moscow 119234;</p><p>1 Leninskie Gori Str., Build. 73A, Moscow 119992</p></bio><xref ref-type="aff" rid="aff-3"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Рыжков</surname><given-names>А. Ю.</given-names></name><name name-style="western" xml:lang="en"><surname>Ryzhkov</surname><given-names>A. Yu.</given-names></name></name-alternatives><bio xml:lang="ru"><p>119992, г. Москва, ул. Ленинские Горы, д.1 стр.40;</p><p>107031, г. Москва, ул. Петровка, 25, стр. 2</p></bio><bio xml:lang="en"><p>1 Leninskie Gori Str., Build. 40, Moscow 119234;</p><p>25 Petrovka Str., Build. 2, 107031 Moscow</p></bio><xref ref-type="aff" rid="aff-4"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Зиновкин</surname><given-names>Р. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Zinovkin</surname><given-names>R. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>119992, г. Москва, ул. Ленинские Горы, д.1 стр.40;</p><p>119992, г. Москва, ул. Ленинские Горы, дом 1 стр. 73А;</p><p>119991, г. Москва, ул. Трубецкая, д. 8, стр. 2</p></bio><bio xml:lang="en"><p>1 Leninskie Gori Str., Build. 40, Moscow 119234;</p><p>1 Leninskie Gori Str., Build. 73A, Moscow 119992;</p><p>8 Trubetskaya Str., Build. 2, 119991 Moscow</p></bio><xref ref-type="aff" rid="aff-5"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>Московский областной научно-исследовательский клинический&#13;
институт им. М. Ф. Владимирского;&#13;
Федеральный научно-клинический центр реаниматологии и реабилитологии</institution><country>Россия</country></aff><aff xml:lang="en"><institution>M. F. Vladimirsky Moscow Regional Research Clinical Institute;&#13;
Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru"><institution>Московский областной научно-исследовательский клинический институт им. М. Ф. Владимирского</institution><country>Россия</country></aff><aff xml:lang="en"><institution>M. F. Vladimirsky Moscow Regional Research Clinical Institute</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-3"><aff xml:lang="ru"><institution>НИИ Физико-химической биологии им. А. Н. Белозерского, Московский государственный университет им. М. В. Ломоносова;&#13;
НИИ Митоинженерии, Московский государственный университет им. М. В. Ломоносова</institution><country>Россия</country></aff><aff xml:lang="en"><institution>A. N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University;&#13;
Institute of Mitoengineering, Lomonosov Moscow State University</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-4"><aff xml:lang="ru"><institution>НИИ Физико-химической биологии им. А. Н. Белозерского, Московский государственный университет им. М. В. Ломоносова;&#13;
Федеральный научно-клинический центр реаниматологии и реабилитологии</institution><country>Россия</country></aff><aff xml:lang="en"><institution>A. N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University;&#13;
Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-5"><aff xml:lang="ru"><institution>НИИ Физико-химической биологии им. А. Н. Белозерского, Московский государственный университет им. М. В. Ломоносова;&#13;
НИИ Митоинженерии, Московский государственный университет им. М. В. Ломоносова;&#13;
Первый Московский государственный медицинский университет им. И. М. Сеченова Минздрава России</institution><country>Россия</country></aff><aff xml:lang="en"><institution>A. N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University;&#13;
Institute of Mitoengineering, Lomonosov Moscow State University;&#13;
I. M. Sechenov First Moscow State Medical University, Ministry of Health of Russia</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2018</year></pub-date><pub-date pub-type="epub"><day>11</day><month>05</month><year>2018</year></pub-date><volume>14</volume><issue>2</issue><fpage>60</fpage><lpage>68</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Гребенчиков О.А., Овезов А.М., Скрипкин Ю.В., Забелина Т.С., Улиткина О.Н., Луговой А.В., Приходько А.С., Рыжков А.Ю., Зиновкин Р.А., 2018</copyright-statement><copyright-year>2018</copyright-year><copyright-holder xml:lang="ru">Гребенчиков О.А., Овезов А.М., Скрипкин Ю.В., Забелина Т.С., Улиткина О.Н., Луговой А.В., Приходько А.С., Рыжков А.Ю., Зиновкин Р.А.</copyright-holder><copyright-holder xml:lang="en">Grebenchikov O.A., Ovezov A.M., Skripkin Y.V., Zabelina T.S., Ulitkina O.N., Lugovoy A.V., Prikhodko A.S., Ryzhkov A.Y., Zinovkin R.A.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://www.reanimatology.com/rmt/article/view/1680">https://www.reanimatology.com/rmt/article/view/1680</self-uri><abstract><p>Цель исследования – изучить эффективность действия синтетического стабилизированного аналога лей-энкефалина в качестве средства, предотвращающего повреждение монослоя эндотелиальных клеток in vitro под действием сывороток пациентов с септическим шоком.</p><sec><title>Материалы и методы</title><p>Материалы и методы. Эксперименты выполнены на монослое эндотелиальных клеток EaHy.926. Изучали влияние синтетического аналога лей-энкефалина in vitro на развитие повреждения клеток под действием сывороток пациентов (5 больных с септическим шоком). Состояние межклеточных контактов эндотелия оценивали методами иммунофлуоресцентной микроскопии и иммуноблотинга с антителами к белку адгезивных контактов — VE-кадгерину и белку плотных контактов — клаудину. Жизнеспособность клеток определяли с помощью окраски йодистым пропидием.</p></sec><sec><title>Результаты</title><p>Результаты. Прекондиционирование синтетическим аналогом лей-энкефалина (10, 50 и 100 мкг/мл) клеток эндотелия in vitro приводило к предотвращению деструкции плотных и адгезивных контактов, а также частично предотвращало гибель эндотелиоцитов.</p></sec><sec><title>Заключение</title><p>Заключение. Прекондиционирование синтетическим аналогом лей-энкефалина частично предотвращает гибель эндотелиоцитов, вызванную воздействием сыворотки септических больных in vitro. Эти данные диктуют необходимость проведения клинических испытаний эффективности применения синтетического аналога лей-энкефалина с целью профилактики сепсис-ассоциированной эндотелиальной дисфункции. </p></sec></abstract><trans-abstract xml:lang="en"><p>The purpose of the study was to determine the efficacy of a synthetic leu-enkephalin stabilized analogue to prevent damage of endothelial cells monolayer in vitro caused by serum samples from septic shock patients.</p><sec><title>Materials and methods</title><p>Materials and methods. The experiments were performed using the EaHy.926 endothelial cells monolayer. We studied the in vitro effect of synthetic leu-enkephalin analogue on the cell damage caused by serum samples from five septic shock patients. The status of endothelial intercellular junctions was estimated by immunofluorescence microscopy and western blot with antibodies against adherens junction protein, VE-cadherin, and against the tight junctions protein, claudin. Cell viability was determined by staining with propidium iodide.</p></sec><sec><title>Results</title><p>Results. Preconditioning with a synthetic leu-enkephalin analogue (10, 50 and 100 μg/ml) of endothelial cells in vitro prevented the destruction of both tight and adherens junction and partially prevented endothelial cell death.</p></sec><sec><title>Conclusion</title><p>Conclusion. Preconditioning with a synthetic leu-enkephalin analogue partially prevents endothelial cell damage caused by exposure to septic patients’ sera in vitro. These data ensure the need for clinical trials on the effectiveness of a synthetic leu-enkephalin analogue for prevention of sepsis-associated endothelial dysfunction in clinics. </p></sec></trans-abstract><kwd-group xml:lang="ru"><kwd>лей-энкефалин</kwd><kwd>проницаемость эндотелия</kwd><kwd>синдром системного воспалительного ответа</kwd><kwd>септический шок</kwd><kwd>Даларгин</kwd></kwd-group><kwd-group xml:lang="en"><kwd>synthetic leu-enkephalin stabilized analogue</kwd><kwd>endothelial permeability</kwd><kwd>systemic inflammatory response syndrome</kwd><kwd>septic shock</kwd><kwd>Dalargin</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Félétou M., Vanhoutte P. Endothelial dysfunction: a multifaceted disorder. Am. J. Physiol. Heart Circ. Physiol. 2006; 291 (3): H985-H1002. DOI: 10.1152/ajpheart.00292.2006. 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