mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-EOR-2935mimmun-2935Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESВлияние рифампицина на экспрессию генов системы Toll-подобных рецепторов в структурах головного мозга крысят с пренатальным воздействием алкоголяEffect of rifampicin on Toll-like receptor system gene expression in brain structures of rats with prenatal alcohol exposurehttps://orcid.org/0000-0002-8318-9069АйрапетовМ. И.AirapetovM. I.

Айрапетов Марат Игоревич - к.м.н., доцент, ведущий научный сотрудник лаборатории биохимической фармакологии; преподаватель кафедры патологической физиологии

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

Тел.: 8 (952) 269-22-20

Marat I. Airapetov, PhD (Medicine), Associate Professor, Leading Research Associate, Laboratory of Biochemical Pharmacology; Lecturer, Department of Pathological Physiology

12 Acad. Pavlov St St. Petersburg 197376

Phone: +7 (952) 269-22-20

interleukin1b@gmail.comhttps://orcid.org/0000-0002-0269-6078ЕрескоС. О.EreskoS. O.

Ереско С.О. – научный сотрудник лаборатории химии и фармакологии лекарственных средств

Санкт-Петербург

Eresko S.O., Research Associate, Laboratory of Chemistry and Pharmacology of Drugs

St. Petersburg

erescko.sergei@yandex.ruМихайловаА. А.MikhailovaA. A.

Михайлова А.А. – студент 4-го курса

Санкт-Петербург

Mikhailova A.A., 4th year Student

St. Petersburg

СухановаД. Д.SukhanovaD. D.

Суханова Д.Д. – студент 4-го курса

Санкт-Петербург

Sukhanova D.D., 4th year Student

St. Petersburg

ИгнатоваП. Д.IgnatovaP. D.

Игнатова П.Д. – студент 5-го курса

Санкт-Петербург

Ignatova P.D., 5th year Student

St. Petersburg

ЛебедевА. А.LebedevA. A.

Лебедев А.А. – д.б.н., профессор, заведующий лабораторией общей фармакологии

Санкт-Петербург

Lebedev A.A., PhD, MD (Biology), Professor, Head, Laboratory of General Pharmacology

St. Petersburg

БычковЕ. Р.BychkovE. R.

Бычков Е.Р. – д.м.н., заведующий лабораторией химии и фармакологии  лекарственных средств

Санкт-Петербург

Bychkov E.R., PhD, MD (Medicine), Head, Laboratory of Chemistry and Pharmacology of Drugs

St. Petersburg

ШабановП. Д.ShabanovP. D.

Шабанов П.Д. – д.м.н., профессор кафедры фармакологии; заведующий отделом нейрофармакологии имени С.В. Аничкова

Санкт-Петербург

Shabanov P.D., PhD, MD (Medicine), Professor, Department of Pharmacology; Head, S. Anichkov Department of Neuropharmacology

St. Petersburg

ФГБНУ «Институт экспериментальной медицины»; ФГБВОУ ВО «Военно-медицинская академия имени С.М. Кирова»РоссияInstitute of Experimental Medicine; S. Kirov Military Medical AcademyRussian FederationФГБНУ «Институт экспериментальной медицины»РоссияInstitute of Experimental MedicineRussian Federation2025080120252717586Copyright © Айрапетов М.И., Ереско С.О., Михайлова А.А., Суханова Д.Д., Игнатова П.Д., Лебедев А.А., Бычков Е.Р., Шабанов П.Д., 20252025Айрапетов М.И., Ереско С.О., Михайлова А.А., Суханова Д.Д., Игнатова П.Д., Лебедев А.А., Бычков Е.Р., Шабанов П.Д.Airapetov M.I., Eresko S.O., Mikhailova A.A., Sukhanova D.D., Ignatova P.D., Lebedev A.A., Bychkov E.R., Shabanov P.D.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/2935

Поступление алкоголя в организм во время беременности может отразиться на нормальном ходе эмбрионального развития плода, что приведет к формированию симптомов фетального алкогольного спектра нарушений (ФАСН). Имеются сведения о том, что при ряде пренатальных патологических состояниях наблюдаются изменения в регуляции механизмов экспрессии ряда про- и противовоспалительных цитокинов. В нашем исследовании мы сосредоточили внимание на изучении уровня экспрессии ряда генов про- и противовоспалительных цитокинов в переднем и височном отделах мозга крысят в постнатальном периоде развития при моделировании пренатального воздействия алкоголя (ПВА). Также оценили уровень экспрессии генов, которые ассоциированы с регуляцией экспрессией генов про- и противовоспалительных цитокинов. Кроме того, в задачи нашего исследования входило произвести фармакологическую коррекцию наблюдаемых изменений потенциальным фармакологическим агентом – рифампицином, который по данным других исследований оказывал нейропротекторный эффект. Моделирование ПВА осуществлялось путем спаивания беременных самок крыс 15%-ным раствором этанола на протяжении всей беременности. Инъекции выполнялись крысятам с 1-го по 7-й постнатальные дни. Забор структур мозга для анализа экспрессии генов осуществлялся на 8-е постнатальные сутки. Результаты исследования показали наличие изменений в экспрессии генов Tlr3 и Tlr4 на 8-е сутки постнатального развития в передней и височной долях головного мозга. Экспрессия генов Myd88 и Ticam имела разнонаправленные изменения среди исследуемых структур мозга крысят с ПВА. Отмечен повышенный уровень мРНК провоспалительных генов. Применение Rif в эксперименте показало способность Rif (50 мг/кг) корректировать наблюдаемые долгосрочные патологические изменения в экспрессии исследуемых генов. Представляется интересным изучение в будущем дозозависимого эффекта, а также исследование выявленных изменений белковыми методами. Кроме того, представляется важным в будущем изучение системы TLR-сигнализации в других структурах мозга с ПВА, а также на разных сроках постнатального развития в онтогенезе.

Alcohol intake during pregnancy may affect the normal course of fetal development, causing the symptoms of fetal alcohol spectrum disorders (FASD). There is evidence that a number of prenatal pathologic conditions exhibit altered expression of several pro- and anti-inflammatory cytokines. In our study, we focused on studying expression of numerous pro- and anti-inflammatory cytokine genes in the forebrain and temporal regions of rat brain during the postnatal development, thus modeling prenatal alcohol exposure effects (PAE). We also evaluated expression of genes associated with regulation of genes controlling expression of pro- and anti-inflammatory cytokines. Moreover, the objectives of our study included pharmacological correction of the observed changes by rifampicin (Rif), a potential pharmacological agent which had a neuroprotective effect shown by other studies,. The experimental model of PAE was produced by oral intake of 15% ethanol solution to pregnant female rats throughout pregnancy. The drug injections were performed to the pups from the 1 to the 7 postnatal days. Brain structures were sampled for gene expression analysis on the 8 postnatal day. The results of the study showed distinct changes in Tlr3 and Tlr4 gene expression in anterior and temporal lobes of brain on the 8 day of postnatal development. Expression of Myd88 and Ticam genes showed multidirectional changes among the studied brain structures of PAE rats. The increased mRNA level of proinflammatory genes was noted. Usage of Rif in experiments showed the ability of Rif (50 mg/kg) to correct the observed long-term pathological changes in the expression of the genes under study. It is of interest to study the dose-dependent effect in the future, as well as to investigate the revealed changes at the level of protein analysis. In future studies, it seems important to evaluate TLR signaling system in other brain structures with PAE, as well as at different terms of postnatal development in ontogenesis.

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