Зависимость антиоксидантного и транскрипционного ответа на периодическую гипоксию от пола и возраста крыс

Аннотация

Периодическая гипоксия – это состояние, характеризующееся чередованием эпизодов недостаточного поступления кислорода (гипоксии) и периодов его нормального или повышенного уровня (реоксигенации). В зависимости от тяжести и длительности воздействия периодическая гипоксия может приводить к активации как защитных, так и патологических механизмов. Целью исследования явилась оценка зависимости эффектов однократной и периодической гипоксии от пола и возраста крыс. В работе использовали самцов и самок крыс Wistar в возрасте 2 и 4 мес. Животных подвергали воздействию нормобарической гипоксии (8% О₂, 2 ч) однократно или ежедневно в течение 5 дней. В дальнейшем у крыс оценивали изменение массы тела, активность и содержание ферментов антиоксидантной системы в плазме крови, а также уровень экспрессии генов HIF‑1α, GPx4, BDNF и CAS‑3 во фронтальной коре, гиппокампе и стриатуме головного мозга. Было показано, что ежедневное воздействие гипоксии приводит к снижению массы тела у самцов и самок крыс обоих возрастов. У самцов зависимые от возраста изменения активности антиоксидантных ферментов и повышение экспрессии генов, маркеров гипоксического воздействия в мозге, наблюдались после однократного воздействия гипоксии. После многократного воздействия регистрируемые показатели не отличались от контрольных значений. У самок использованное воздействие не влияло на активность антиоксидантных ферментов, а увеличение экспрессии исследуемых генов наблюдалось только после 5‑кратного воздействия гипоксии. Проведённые эксперименты выявили значительные различия в ответе на однократное и периодическое воздействие гипоксии у самцов и самок крыс. Полученные данные необходимо учитывать при разработке экспериментальных моделей периодической гипоксии и исследовании механизмов адаптивных и патологических реакций организма на повторяющуюся гипоксию/реоксигенацию.

Сноски

* Адресат для корреспонденции.

Вклад авторов

Н.Г. Левицкая, Е.А. Себенцова – концепция и руководство работой; С.Д. Кабиольская, О.И. Патявина, И.А. Кабиольский, О.К. Савушкина, Е.Б. Терешкина, Т.А. Прохорова – проведение экспериментов; С.Д. Кабиольская, Н.Г. Левицкая – обсуждение результатов исследования; С.Д. Кабиольская, И.А. Кабиольский, Е.А. Себенцова, Н.Г. Левицкая – написание и редактирование текста.

Финансирование

Работа выполнена с привлечением средств государственного задания кафедры физиологии человека и животных биологического факультета МГУ имени М.В. Ломоносова: 28-3-21(№ 121032300071-8) «Механизмы физиологических адаптаций» и государственного задания ФГБНУ НЦПЗ: FURU-2024-0016 (№ 124020700032-9) «Биологические маркеры психических и нейродегенеративных заболеваний: фундаментальные и прикладные аспекты».

Конфликт интересов

Авторы заявляют об отсутствии конфликта интересов.

Соблюдение этических норм

Исследование проведено с соблюдением биоэтических норм обращения с экспериментальными животными в соответствии с «Правилами надлежащей лабораторной практики» (Приказ МЗ РФ № 199 от 01.04.2016) и требованиями Директивы 2010/63/EU Европейского парламента от 22.09.2010. Условия содержания животных и экспериментальные процедуры одобрены Комиссией по биоэтике МГУ (заявки № 157-ж-2 от 22.06.2023 и № 12.5-сод от 24.10.2024).

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