<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.3 20210610//EN" "JATS-journalpublishing1-3.dtd">
<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">scbmt</journal-id><journal-title-group><journal-title xml:lang="ru">БИОМЕДИЦИНА</journal-title><trans-title-group xml:lang="en"><trans-title>Journal Biomed</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2074-5982</issn><issn pub-type="epub">2713-0428</issn><publisher><publisher-name>Scientific center of biomedical technologies of Federal Medical and Biological Agency</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.33647/2074-5982-16-4-24-33</article-id><article-id custom-type="elpub" pub-id-type="custom">scbmt-1215</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>РЕЛЕВАНТНОЕ И АЛЬТЕРНАТИВНОЕ БИОМОДЕЛИРОВАНИЕ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>RELEVANT AND ALTERNATIVE BIOMODELLING</subject></subj-group></article-categories><title-group><article-title>Модель фатального острого поражения легких и острого респираторного дистресс-синдрома</article-title><trans-title-group xml:lang="en"><trans-title>A Model of Fatal Acute Lung Injury and Acute Respiratory Distress Syndrome</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>Помыткин</surname><given-names>И. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Pomytkin</surname><given-names>I. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Помыткин Игорь Анатольевич, к.х.н.</p><p>143442, Московская обл., Красногорский р-н, п. Светлые горы, владение 1</p></bio><bio xml:lang="en"><p>Igor A. Pomytkin, Cand. Sci. (Chem.)</p><p>143442, Moscow region, Krasnogorsk district, Svetlye gory village, building 1</p></bio><email xlink:type="simple">ipomytkin@mail.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>Каркищенко</surname><given-names>В. Н.</given-names></name><name name-style="western" xml:lang="en"><surname>Karkischenko</surname><given-names>V. N.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Каркищенко Владислав Николаевич, д.м.н., проф.</p><p>143442, Московская обл., Красногорский р-н, п. Светлые горы, владение 1</p></bio><bio xml:lang="en"><p>Vladislav N. Karkischenko, Dr. Sci. (Med.), Prof.</p><p>143442, Moscow region, Krasnogorsk district, Svetlye gory village, building 1</p></bio><email xlink:type="simple">scbmt@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>Фокин</surname><given-names>Ю. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Fokin</surname><given-names>Yu. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Фокин Юрий Владимирович, к.б.н.</p><p>143442, Московская обл., Красногорский р-н, п. Светлые горы, владение 1</p></bio><bio xml:lang="en"><p>Yuriy V. Fokin, Cand. Sci. (Biol.)</p><p>143442, Moscow region, Krasnogorsk district, Svetlye gory village, building 1</p></bio><email xlink:type="simple">fokin@scbmt.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>Нестеров</surname><given-names>М. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Nesterov</surname><given-names>M. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Нестеров Максим Сергеевич</p><p>143442, Московская обл., Красногорский р-н, п. Светлые горы, владение 1</p></bio><bio xml:lang="en"><p>Maxim S. Nesterov</p><p>143442, Moscow region, Krasnogorsk district, Svetlye gory village, building 1</p></bio><email xlink:type="simple">mdulya@gmail.com</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>Петрова</surname><given-names>Н. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Petrova</surname><given-names>N. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Петрова Наталья Владимировна</p><p>143442, Московская обл., Красногорский р-н, п. Светлые горы, владение 1</p></bio><bio xml:lang="en"><p>Nataliya V. Petrova</p><p>143442, Moscow region, Krasnogorsk district, Svetlye gory village, building 1</p></bio><email xlink:type="simple">m-sklad@yandex.ru</email><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>ФГБУН «Научный центр биомедицинских технологий Федерального медико-биологического агентства России»</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Scientiﬁc Center of Biomedical Technologies of the Federal Medical and Biological Agency of Russia</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2020</year></pub-date><pub-date pub-type="epub"><day>16</day><month>10</month><year>2020</year></pub-date><volume>16</volume><issue>4</issue><fpage>24</fpage><lpage>33</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Помыткин И.А., Каркищенко В.Н., Фокин Ю.В., Нестеров М.С., Петрова Н.В., 2020</copyright-statement><copyright-year>2020</copyright-year><copyright-holder xml:lang="ru">Помыткин И.А., Каркищенко В.Н., Фокин Ю.В., Нестеров М.С., Петрова Н.В.</copyright-holder><copyright-holder xml:lang="en">Pomytkin I.A., Karkischenko V.N., Fokin Y.V., Nesterov M.S., Petrova N.V.</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://journal.scbmt.ru/jour/article/view/1215">https://journal.scbmt.ru/jour/article/view/1215</self-uri><abstract><p>Настоящая работа посвящена разработке экспериментальной фатальной модели острого поражения легких и острого респираторного дистресс-синдрома (ОРДС) на мышах линии C57Bl/6Y. Модель основана на интратрахеальном введении бактериального липополисахарида (ЛПС) с добавлением иммуномодуляторов мурамилпептида и полного адъюванта Фрейнда мышам, предварительно сенсибилизированным α-галактозилцерамидом. Модель характеризуется диффузным альвеолярным поражением легких, высокой летальностью, многократным повышением мРНК и белка интерлейкина-6 в тканях легкого и может быть использована для оценки эффективности потенциальных средств лечения острого поражения легких и острого респираторного дистресс-синдрома, в т. ч. воспроизводящего существенные признаки ОРДС при COVID-19.</p></abstract><trans-abstract xml:lang="en"><p>This study was aimed at developing an experimental model of fatal acute lung injury and acute respiratory distress syndrome (ARDS) based on the intratracheal administration of bacterial lipopolysaccharide (LPS) in combination with muramylpeptide and Freund’s complete adjuvant to C57Bl/6Y mice sensitized with α-galactosylceramide. The developed model is characterized by diffuse alveolar damage to the lungs and high mortality rates, as well as by a multifold increase in the mRNA level of interleukin-6 in the lungs. The model can be used for assessing the efﬁcacy of drug candidates in the treatment of acute lung injury and ARDS, including in COVID-19.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>острое поражение легких</kwd><kwd>острый респираторный дистресс-синдром</kwd><kwd>мыши линии C57Bl/6Y</kwd><kwd>«цитокиновый шторм»</kwd><kwd>интерлейкин-6</kwd><kwd>COVID-19</kwd></kwd-group><kwd-group xml:lang="en"><kwd>acute lung injury</kwd><kwd>acute respiratory distress syndrome</kwd><kwd>C57Bl/6Y mice line</kwd><kwd>“cytokine storm”</kwd><kwd>interleukin-6</kwd><kwd>COVID-19</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">Каркищенко Н.Н. Альтернативы биомедицины. Т. 1. Основы биомедицины и фармакомоделирования. М.: Изд-во ВПК, 2007. 320 с.</mixed-citation><mixed-citation xml:lang="en">Karkischenko N.N. Al’ternativy biomediciny. T. 1. Osnovy biomediciny i farmakomodelirovaniya [Biomedicine alternatives. Vol. 1. Fundamentals of biomedicine and pharmaco-modeling]. Moscow: Izdatel’stvo VPK, 2007. 320 p. (In Russian).</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Каркищенко Н.Н. Основы биомоделирования. М.: Межакадемическое изд-во ВПК, 2004. 607 с.</mixed-citation><mixed-citation xml:lang="en">Karkischenko N.N. Osnovy biomodelirovaniya [Basics of biomodeling]. Moscow: Mezhakademicheskoye Izdatel’stvo VPK, 2004. 607 p. (In Russian).</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Руководство по лабораторным животным и альтернативным моделям в биомедицинских исследованиях / Под ред. Н.Н. Каркищенко и др. М.: Профиль-2С, 2010. 358 p.</mixed-citation><mixed-citation xml:lang="en">Rukovodstvo po laboratornym zhivotnym i al’ternativnym modelyam v biomedicinskih issledovaniyah [Manual on laboratory animals and alternative models in biomedical research]. Ed. by N.N. Karkischenko, et al. Moscow: Proﬁl’-2S Publ., 2010. 358 p. (In Russian).</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Aoyagi T., Yamamoto N., Hatta M., Tanno D., Miyazato A., Ishii K., et al. Activation of pulmonary invariant NKT cells leads to exacerbation of acute lung injury caused by LPS through local production of IFN-γ and TNF-α by Gr-1+ monocytes. Int. Immunol. 2011;23(2):97–108.</mixed-citation><mixed-citation xml:lang="en">Aoyagi T., Yamamoto N., Hatta M., Tanno D., Miyazato A., Ishii K., et al. Activation of pulmonary invariant NKT cells leads to exacerbation of acute lung injury caused by LPS through local production of IFN-γ and TNF-α by Gr-1+ monocytes. Int. Immunol. 2011;23(2):97–108.</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Bacci M.R., Leme R.C., Zing N.P., Murad N., Adami F., Hinnig P.F., et al. IL-6 and TNF-α serum levels are associated with early death in community-acquired pneumonia patients. Braz. J. Med. Biol. Res. 2015;48(5):427–432.</mixed-citation><mixed-citation xml:lang="en">Bacci M.R., Leme R.C., Zing N.P., Murad N., Adami F., Hinnig P.F., et al. IL-6 and TNF-α serum levels are associated with early death in community-acquired pneumonia patients. Braz. J. Med. Biol. Res. 2015;48(5):427–432.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Celli B.R., Locantore N., Yates J., Tal-Singer R., Miller B.E., Bakke P., et al. ECLIPSE Investigators. Inﬂammatory biomarkers improve clinical prediction of mortality in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 2012;185(10):1065–1072.</mixed-citation><mixed-citation xml:lang="en">Celli B.R., Locantore N., Yates J., Tal-Singer R., Miller B.E., Bakke P., et al. ECLIPSE Investigators. Inﬂammatory biomarkers improve clinical prediction of mortality in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 2012;185(10):1065–1072.</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Crosby C.M., Kronenberg M. Tissue-speciﬁc functions of invariant natural killer T cells. Nat. Rev. Immunol. 2018;18(9):559–574.</mixed-citation><mixed-citation xml:lang="en">Crosby C.M., Kronenberg M. Tissue-speciﬁc functions of invariant natural killer T cells. Nat. Rev. Immunol. 2018;18(9):559–574.</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">D’Alessio F.R. Mouse Models of Acute Lung Injury and ARDS. Methods Mol. Biol. 2018;1809:341–350.</mixed-citation><mixed-citation xml:lang="en">D’Alessio F.R. Mouse Models of Acute Lung Injury and ARDS. Methods Mol. Biol. 2018;1809:341–350.</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Davey R.T. Jr., Lynﬁeld R., Dwyer D.E., Losso M.H., Cozzi-Lepri A., Wentworth D., et al. INSIGHT FLU 002 &amp; 003 Study Groups. The association between serum biomarkers and disease outcome in inﬂuenza A(H1N1)pdm09 virus infection: results of two international observational cohort studies. PLoS One. 2013;8(2):e57121.</mixed-citation><mixed-citation xml:lang="en">Davey R.T. Jr., Lynﬁeld R., Dwyer D.E., Losso M.H., Cozzi-Lepri A., Wentworth D., et al. INSIGHT FLU 002 &amp; 003 Study Groups. The association between serum biomarkers and disease outcome in inﬂuenza A(H1N1)pdm09 virus infection: results of two international observational cohort studies. PLoS One. 2013;8(2):e57121.</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Gubernatorova E.O., Gorshkova E.A., Polinova A.I., Drutskaya M.S. IL-6: Relevance for immunopathology of SARS-CoV-2. Cytokine Growth Factor Rev. 2020;53:13–24.</mixed-citation><mixed-citation xml:lang="en">Gubernatorova E.O., Gorshkova E.A., Polinova A.I., Drutskaya M.S. IL-6: Relevance for immunopathology of SARS-CoV-2. Cytokine Growth Factor Rev. 2020;53:13–24.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Henry B.M., de Oliveira M.H.S., Benoit S., Plebani M., Lippi G. Hematologic, biochemical and immune biomarker abnormalities associated with severe illness and mortality in coronavirus disease 2019 (COVID-19): a meta-analysis. Clin. Chem. Lab. Med. 2020;58(7):1021–1028.</mixed-citation><mixed-citation xml:lang="en">Henry B.M., de Oliveira M.H.S., Benoit S., Plebani M., Lippi G. Hematologic, biochemical and immune biomarker abnormalities associated with severe illness and mortality in coronavirus disease 2019 (COVID-19): a meta-analysis. Clin. Chem. Lab. Med. 2020;58(7):1021–1028.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Kudo D., Toyama M., Aoyagi T., Akahori Y., Yamamoto H., Ishii K., et al. Involvement of high mobility group box 1 and the therapeutic effect of recombinant thrombomodulin in a mouse model of severe acute respiratory distress syndrome. Clin. Exp. Immunol. 2013;173(2):276–287.</mixed-citation><mixed-citation xml:lang="en">Kudo D., Toyama M., Aoyagi T., Akahori Y., Yamamoto H., Ishii K., et al. Involvement of high mobility group box 1 and the therapeutic effect of recombinant thrombomodulin in a mouse model of severe acute respiratory distress syndrome. Clin. Exp. Immunol. 2013;173(2):276–287.</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Liu T., Zhang L., Joo D., Sun S.C. NF-κB signaling in inﬂammation. Signal Transduct. Target. Ther. 2017;2. DOI: 10.1038/sigtrans.2017.23.</mixed-citation><mixed-citation xml:lang="en">Liu T., Zhang L., Joo D., Sun S.C. NF-κB signaling in inﬂammation. Signal Transduct. Target. Ther. 2017;2. DOI: 10.1038/sigtrans.2017.23.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">McGonagle D., Sharif K., O’Regan A., Bridgewood C. The Role of Cytokines including Interleukin-6 in COVID-19 induced Pneumonia and Macrophage Activation Syndrome-Like Disease. Autoimmun. Rev. 2020;19(6):102537.</mixed-citation><mixed-citation xml:lang="en">McGonagle D., Sharif K., O’Regan A., Bridgewood C. The Role of Cytokines including Interleukin-6 in COVID-19 induced Pneumonia and Macrophage Activation Syndrome-Like Disease. Autoimmun. Rev. 2020;19(6):102537.</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Ogawa C., Liu Y.J., Kobayashi K.S. Muramyl dipeptide and its derivatives: peptide adjuvant in immunological disorders and cancer therapy. Curr. Bioact. Compd. 2011;7(3):180–197.</mixed-citation><mixed-citation xml:lang="en">Ogawa C., Liu Y.J., Kobayashi K.S. Muramyl dipeptide and its derivatives: peptide adjuvant in immunological disorders and cancer therapy. Curr. Bioact. Compd. 2011;7(3):180–197.</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Potey P.M., Rossi A.G., Lucas C.D., Dorward D.A. Neutrophils in the initiation and resolution of acute pulmonary inﬂammation: understanding biological function and therapeutic potential. J. Pathol. 2019;247(5):672–685.</mixed-citation><mixed-citation xml:lang="en">Potey P.M., Rossi A.G., Lucas C.D., Dorward D.A. Neutrophils in the initiation and resolution of acute pulmonary inﬂammation: understanding biological function and therapeutic potential. J. Pathol. 2019;247(5):672–685.</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Rincon M., Irvin C.G. Role of IL-6 in asthma and other inﬂammatory pulmonary diseases. Int. J. Biol. Sci. 2012;8(9):1281–1290.</mixed-citation><mixed-citation xml:lang="en">Rincon M., Irvin C.G. Role of IL-6 in asthma and other inﬂammatory pulmonary diseases. Int. J. Biol. Sci. 2012;8(9):1281–1290.</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Zhao J., Li X., Gao Y., Huang W. Risk factors for the exacerbation of patients with 2019 Novel Coronavirus: A meta-analysis. Int. J. Med. Sci. 2020;17(12):17441750.</mixed-citation><mixed-citation xml:lang="en">Zhao J., Li X., Gao Y., Huang W. Risk factors for the exacerbation of patients with 2019 Novel Coronavirus: A meta-analysis. Int. J. Med. Sci. 2020;17(12):17441750.</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
