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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">phkinetica</journal-id><journal-title-group><journal-title xml:lang="ru">Фармакокинетика и Фармакодинамика</journal-title><trans-title-group xml:lang="en"><trans-title>Pharmacokinetics and Pharmacodynamics</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2587-7836</issn><issn pub-type="epub">2686-8830</issn><publisher><publisher-name>ООО «Издательство ОКИ»</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.37489/2587-7836-2023-3-82-93</article-id><article-id custom-type="elpub" pub-id-type="custom">phkinetica-385</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>ДОКЛИНИЧЕСКИЕ ИССЛЕДОВАНИЯ ФАРМАКОДИНАМИКИ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>PRECLINICAL PHARMACODYNAMICS STUDIES</subject></subj-group></article-categories><title-group><article-title>Изучение взаимосвязи между тяжестью течения алкогольной кардиомиопатии и уровнем потребления алкоголя у самцов и самок крыс на модели «бытового пьянства»</article-title><trans-title-group xml:lang="en"><trans-title>Study of the relationship between the severity of alcoholic cardiomyopathy and the level of alcohol consumption in male and female rats in the model of “home drinking”</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-2832-4739</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Крыжановский</surname><given-names>С. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Kryzhanovskii</surname><given-names>S. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Крыжановский Сергей Александрович - д. м. н., зав. лабораторией фармакологического скрининга</p><p>Москва</p></bio><bio xml:lang="en"><p>Sergey А. Kryzhanovskii - Dr. Sci (Med.), Head of laboratory of pharmacological screening</p><p>Moscow</p></bio><email xlink:type="simple">SAK-538@yandex.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-3988-7724</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Цорин</surname><given-names>И. Б.</given-names></name><name name-style="western" xml:lang="en"><surname>Tsorin</surname><given-names>I. B.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Цорин Иосиф Борисович -д. б. н., в. н. с. лаборатории фармакологического скрининга</p><p>Москва</p></bio><bio xml:lang="en"><p>Iosif B. Tsorin - Dr. Sci. (Biol.), Leading researcher of laboratory of pharmacological screening</p><p>Moscow</p></bio><email xlink:type="simple">tsorinib@yandex.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-0154-722X</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Ионова</surname><given-names>Е. О.</given-names></name><name name-style="western" xml:lang="en"><surname>Ionova</surname><given-names>E. O.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Ионова Екатерина Олеговна - м. н. с. лаборатории фармакологического скрининга</p><p>Scopus Author ID: 55507470600</p><p>Москва</p></bio><bio xml:lang="en"><p>Ekaterina O. Ionova - Junior Research Scientist of Laboratory of Pharmacological Screening</p><p>Moscow</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-4229-3107</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Барчуков</surname><given-names>В. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Barchukov</surname><given-names>V. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Барчуков Владимир Валерьевич - н. с. лаборатории фармакологического скрининга</p><p>Москва</p></bio><bio xml:lang="en"><p>Vladimir V. Barchukov - Research scientist of laboratory of pharmacological screening</p><p>Moscow</p></bio><email xlink:type="simple">barchukov.pharm@yandex.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-4779-427X</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Столярук</surname><given-names>В. Н.</given-names></name><name name-style="western" xml:lang="en"><surname>Stolyaruk</surname><given-names>V. N.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Столярук Валерий Николаевич - к. м. н., с. н. с. лаборатории фармакологического скрининга</p><p>Москва</p></bio><bio xml:lang="en"><p>Valeriy N. Stolyaruk -PhD, Cand. Sci. (Med.), Senior researcher scientist of laboratory of pharmacological screening</p><p>Moscow</p></bio><email xlink:type="simple">vns539@yandex.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-7407-7516</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Вититнова</surname><given-names>М. Б.</given-names></name><name name-style="western" xml:lang="en"><surname>Vititnova</surname><given-names>M. B.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Вититнова Марина Борисовна - к. б. н., с. н. с. лаборатории фармакологического скрининга</p><p>Москва</p></bio><bio xml:lang="en"><p>Marina B. Vititnova - PhD, Cand. Sci. (Biol.), Senior researcher scientist of laboratory of pharmacological screening</p><p>Moscow</p></bio><email xlink:type="simple">MB-Vit@yandex.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-9847-8058</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Колик</surname><given-names>Л. Г.</given-names></name><name name-style="western" xml:lang="en"><surname>Kolik</surname><given-names>L. G.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Колик Лариса Геннадьевна - д. б. н., проф. РАН, руководитель лаборатории фармакологической регуляции состояний зависимости</p><p>Москва</p></bio><bio xml:lang="en"><p>Larisa G. Kolik - Dr. Sci. (Biol.), Professor RAS, head of the Laboratory of Pharmacological regulation of addiction conditions</p><p>Moscow</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-0218-8580</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Дурнев</surname><given-names>А. Д.</given-names></name><name name-style="western" xml:lang="en"><surname>Durnev</surname><given-names>A. D.</given-names></name></name-alternatives><bio xml:lang="ru"><p>урнев Андрей Дмитриевич - д. м. н., профессор, член-корр. РАН, зав. отделом лекарственной токсикологии</p><p>Москва</p></bio><bio xml:lang="en"><p>Andrei D. Durnev - Dr. Sci. (Med.), professor, corresponding member RAS, Head of the department of drug toxicology</p><p>Moscow</p></bio><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru">ФГБНУ «НИИ фармакологии имени В.В. Закусова»<country>Россия</country></aff><aff xml:lang="en">FSBI "Research Zakusov Institue of Pharmacology"<country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2023</year></pub-date><pub-date pub-type="epub"><day>03</day><month>11</month><year>2023</year></pub-date><volume>0</volume><issue>3</issue><fpage>82</fpage><lpage>93</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Крыжановский С.А., Цорин И.Б., Ионова Е.О., Барчуков В.В., Столярук В.Н., Вититнова М.Б., Колик Л.Г., Дурнев А.Д., 2023</copyright-statement><copyright-year>2023</copyright-year><copyright-holder xml:lang="ru">Крыжановский С.А., Цорин И.Б., Ионова Е.О., Барчуков В.В., Столярук В.Н., Вититнова М.Б., Колик Л.Г., Дурнев А.Д.</copyright-holder><copyright-holder xml:lang="en">Kryzhanovskii S.A., Tsorin I.B., Ionova E.O., Barchukov V.V., Stolyaruk V.N., Vititnova M.B., Kolik L.G., Durnev A.D.</copyright-holder><license 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.pharmacokinetica.ru/jour/article/view/385">https://www.pharmacokinetica.ru/jour/article/view/385</self-uri><abstract><sec><title>Введение</title><p>Введение. Ранее на разработанной нами трансляционной модели алкогольной кардиомиопатии (АКМП) у беспородных белых крыс, воспроизводящей основные клинико-диагностические признаки этого заболевания, показано, что у крыс обоего пола в условиях постоянной 24/7 алкоголизации в течение 24 недель формируется АКМП.</p><p>Цель настоящего исследования — сравнительная оценка особенностей формирования АКМП у самцов и самок крыс в зависимости от уровня потребления этанола в модельных экспериментах, имитирующих «бытовое пьянство», при периодической алкоголизации 24/2 в течение 24 недель.</p></sec><sec><title>Материалы и методы</title><p>Материалы и методы. Эксперименты выполнены на беспородных белых крысах, рандомизированных на 4 группы: 1-я группа — контрольные крысы-самцы (n = 18), 2-я группа — контрольные крысы-самки (n = 18), 3-я группа — алкоголизированные крысы-самцы (n = 39) и 4-я группа — алкоголизированные крысы-самки (n = 19). Контрольные животные получали обычный рацион питания и свободный доступ к воде. Животные 3-й и 4-й групп еженедельно, в течение 24 недель, с 22:00 пятницы по 8:00 понедельника в качестве единственного источника жидкости получали 10 % раствор этанола при неограниченном доступе к стандартному корму, а в остальные дни обычный рацион.</p></sec><sec><title>Результаты</title><p>Результаты. У животных обоего пола через 24 недели от начала потребления раствора этанола формируется АКМП, о чем свидетельствует увеличение конечно-систолического и конечно-диастолического размеров левого желудочка сердца (p = 0,0001) и снижение его фракции выброса (p = 0,0001), при этом степень патологического ремоделирования миокарда более выражена у самок. Согласно кластерному анализу, по потреблению этанола (ПЭ) животные обоего пола подразделяются на 3 подгруппы: низкое, среднее и высокое ПЭ, однако у самцов превалирует подгруппа со средним ПЭ — 56 %, а у самок с высоким ПЭ — 47 % (р = 0,0286), подгруппа с низким ПЭ минимальна (16 %). При этом, если у самцов во всех подгруппах, начиная с 8-й недели алкоголизации, ПЭ динамически снижается, то у самок в подгруппах со средним и высоким ПЭ оно, начиная с 16-й недели, возрастает. Установлено, что степень ремоделирования левого желудочка сердца у самок с высоким и средним ПЭ почти в 2 раза выше, чем у самцов (p &lt; 0,05).</p></sec><sec><title>Заключение</title><p>Заключение. В модельных экспериментах, имитирующих «бытовое пьянство», показано, что у самок интенсивность ремоделирования левого желудочка сердца значимо больше, чем у самцов, что, по-видимому, определяется выявленными зависимыми от пола разнонаправленными тенденциями в формировании алкогольного поведения, характеризующегося динамическим ростом потребления этанола у самок крыс по мере нарастания сроков алкоголизации.</p></sec></abstract><trans-abstract xml:lang="en"><sec><title>Background</title><p>Background. Earlier, on the translational model of alcoholic cardiomyopathy (ACMP) developed by us in outbred white rats, which reproduces the main clinical diagnostic signs of this disease, it was shown that in rats of both sexes under conditions of constant 24/7 alcoholization for 24 weeks, AСMP is formed.</p><p>This study purpose is a comparative assessment of the features of the ACM formation in male and female rats depending on the level of ethanol consumption in model experiments simulating "domestic drunkenness" with periodic alcoholization 24/2 for 24 weeks.</p></sec><sec><title>Materials and methods</title><p>Materials and methods. Experiments were performed on outbred white rats randomized into 4 groups: group 1 — control male rats (n=18), group 2 — control female rats (n = 18), group 3 — alcoholized male rats (n = 39) and group 4 — alcoholized female rats (n = 19). Control animals received a normal diet and free access to water. Animals of the 3rd and 4th groups weekly, for 24 weeks, from Friday 22.00 to Monday 8.00, received a 10 % ethanol solution as the only source of liquid with unlimited access to standard food, and the usual diet on the remaining days.</p></sec><sec><title>Results</title><p>Results. In animals of both sexes, after 24 weeks from the consumption start of the ethanol solution, ACM is formed, as evidenced by an increase in the end-systolic and end-diastolic sizes of the left ventricle of the heart (p = 0.0001) and a decrease in its ejection fraction (p = 0.0001), while the degree of pathological myocardial remodeling is more pronounced in females. According to cluster analysis, by the consumption of ethanol (CET), animals of both sexes are divided into 3 subgroups: low, medium and high CET, however, in males, the subgroup with an average CET prevails — 56 %, and in females with a high CET — 47 % (p = 0.0286), the low CET subgroup is minimal (16 %). At the same time, if in males in all subgroups, starting from the 8th week of alcoholization, CET dynamically decreases, then how in females in subgroups with medium and high CET, starting from the 16th week, it increases. It was found that the degree of left ventricular remodeling in females with high and moderate CET was almost 2 times higher than in males (p &lt; 0.05).</p></sec><sec><title>Conclusion</title><p>Conclusion. In model experiments imitating “domestic drunkenness”, it was shown that in females the intensity of the left ventricle heart remodeling is signiﬁcantly higher than in males, which, apparently, is determined by the identiﬁed gender-dependent multidirectional trends in the formation of alcoholic behavior characterized by dynamic growth. consumption of ethanol in female rats as the duration of alcoholization increases.</p></sec></trans-abstract><kwd-group xml:lang="ru"><kwd>крысы самцы и самки</kwd><kwd>алкогольная кардиомиопатия</kwd><kwd>эхокардиография</kwd><kwd>ремоделирование</kwd><kwd>потребление этанола</kwd><kwd>половые различия</kwd></kwd-group><kwd-group xml:lang="en"><kwd>male and female rats</kwd><kwd>alcoholic cardiomyopathy</kwd><kwd>echocardiography</kwd><kwd>remodeling</kwd><kwd>ethanol consumption</kwd><kwd>sex diﬀerences</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">Отчёт ВОЗ «Мониторинг здоровья» за 2018 год. 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