Аннотация
Для разработки подходов к лечению ишемических поражений мозга важно понимание механизмов регуляции апоптотической и аутофагической гибели нейронов. При сильно выраженном ишемическом (или другом патологическом) воздействии нейроны могут гибнуть от активации и апоптоза, и аутофагии. Целью работы является оценка вклада активации аутофагии и апоптоза в гибель нейронов CA1 района гиппокампа и лобной коры мозга крыс при двухсосудистой ишемии переднего мозга и гипотензии и последующей длительной реперфузии, а также изучение способности инсулина, введенного интраназально, предотвращать аутофагическую и апоптотическую гибель нейронов. Ингибитор аутофагии 3-метиладенин или ингибитор апоптоза Ac-DEVD-CHO или фосфатный буфер вводили крысам интрацеребровентрикулярно до ишемии и реперфузии. Для подсчета количества живых нейронов срезы мозга окрашивали по Нисслю. При ишемии и реперфузии число живых нейронов в CA1 районе гиппокампа снижалось до 58.3±1.5% от их содержания у ложно-оперированных крыс (контроль, принятый за 100%). Введение крысам ингибитора аутофагии или апоптоза увеличивало число живых нейронов в районе CA1 гиппокампа c 58.3±1.5 % до 90.4±2.2% (p<0.001) и 71.6± 1.8% (p<0.001) от контроля, соответственно. Введение крысам 0.5 МЕ инсулина (до ишемии и ежедневно в течение 7 дней при реперфузии) нормализовало число живых нейронов в CA1 районе гиппокампа до 100.2±1.9% от контроля. В лобной коре мозга также наблюдалось снижение жизнеспособности нейронов при ишемии и реперфузии и ее повышение при введении ингибиторов аутофагии и апоптоза и в большей степени при введении инсулина. Отличие заключалось в меньшей чувствительности нейронов коры мозга, чем нейронов гиппокампа к ишемии и реперфузии. Полученные данные свидетельствуют о способности инсулина, введенного интраназально, уменьшать гибель нейронов мозга, вызванную активацией аутофагии и апоптоза, при ишемии мозга и реперфузии.
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