Аннотация
Найдено, что ишемия и последующая трехдневная реперфузия переднего мозга приводят к увеличению уровня маркера аутофагии LC3B-II, уровня глиального фибриллярного кислого белка (GFAP) и активации каспазы-3 в гиппокампе и лобной коре мозга крыс. При этом интраназальное введение крысам с ишемией и реперфузией мозга 0.5 МЕ инсулина (до ишемии и ежедневно при реперфузии) достоверно и значительно снижает уровень LC3B-II и активность каспазы-3 в изучаемых структурах. Это показывает способность инсулина ингибировать активацию аутофагии и апоптоза в переднем мозге при его ишемии и реперфузии. Не удалось выявить достоверного снижения уровня GFAP в этих районах мозга под влиянием введения животным инсулина. Показано, что интраназальное введение инсулина активирует протеинкиназу Akt (активирующую комплекс mTORС1, ингибирующий процессы аутофагии) и ингибирует протеинкиназу AMPK (инициируюшую процессы аутофагии) в гиппокампе и коре мозга крыс, что, очевидно, лежит в основе его способности снижать аутофагическую и апоптотическую гибель нейронов. Данные о модуляции инсулином активности протеинкиназ Akt и AMPK в опытах in vivo согласуются с результатами исследованиями возможного механизма нейропротекторного действия инсулина, проведенными нами ранее in vitro на нейронах коры мозга в состоянии окислительного стресса.
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