Российский физиологический журнал им. И.М. Сеченова, 2023, T. 109, № 7, стр. 872-889

Вклад активности SERCA в изменение сократительных характеристик m. soleus крыс при функциональной разгрузке

К. А. Шарло 1, И. Д. Львова 1, С. А. Тыганов 1, К. А. Зарипова 1, С. П. Белова 1, Т. Л. Немировская 1*

1 Институт медико-биологических проблем
Москва, Россия

* E-mail: Nemirovskaya@bk.ru

Поступила в редакцию 05.05.2023
После доработки 29.05.2023
Принята к публикации 29.05.2023

Аннотация

Нарушение функций скелетных мышц и их атрофия при функциональной разгрузке сопровождаются накоплением избыточного кальция в миоплазме мышечных волокон. Мы предположили, что накопление кальция может происходить, кроме прочих механизмов, из-за ингибирования работы Ca2+-АТФазы сарко/эндоплазматического ретикулума (SERCA) при разгрузке мышц. В этом случае применение активатора SERCA будет снижать уровень кальция в миоплазме и предотвращать последствия функциональной разгрузки. Самцы крыс были распределены на 3 группы – виварный контроль с введением плацебо (С, n = 8), группа 7-суточного вывешивания с введением плацебо (7НS, n = 8) и группа 7-суточного вывешивания с введением внутрибрюшинно активатора SERCA CDN1163 (50 мг/кг (7HS+CDN), n = 8). Одну m. soleus каждой крысы замораживали в жидком азоте, вторую тестировали на функциональные свойства. В группе 7HS обнаружили повышенную утомляемость soleus в тесте ex vivo, существенное увеличение мРНК и количества быстрых мышечных волокон, рост уровня кальций-зависимого фосфорилирования CaMK II и уровня окисления тропомиозина, а также снижение содержания митохондриальной ДНК и белка. Все эти изменения были предотвращены в группе с введением активатора SERCA CDN1163. Вывод: 7-суточное введение активатора SERCA предотвращает снижение индекса утомления m. soleus, вероятно, за счет предотвращения снижения количества волокон I типа и маркеров митохондриального биогенеза. Введение активатора SERCA не замедляет развития атрофии m. soleus.

Ключевые слова: функциональная разгрузка m. soleus, атрофия, утомляемость m. soleus, типы мышечных волокон, NFATC1, митохондриальная ДНК, митофузин ½

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