Нейрональная NO-синтаза в патогенезе метаболического синдрома

Метаболический синдром (МС), который характеризуется ожирением, гипертонией, дислипидемией, резистентностью к инсулину, приобрел в последние годы характер эпидемии. Вследствие этого изучение молекулярных механизмов, лежащих в основе развития МС и его осложнений, а также поиск новых терапевтических средств для их лечения являются одними из острейших проблем современной эндокринологии. В последние годы получены убедительные свидетельства того, что ключевую роль среди молекулярных причин МС играют функциональные изменения экспрессии, активности и регуляторных свойств нейрональной NO-синтазы (nNOS), катализирующей образование важнейшего вторичного посредника – оксида азота (NO), и зависимых от нее NO/цГМФ-сигнальных путей в мозге, миокарде и скелетных мышцах. В мозге nNOS ассоциирована с NMDA-рецепторами, гиперактивация которых при МС сопровождается избыточной стимуляцией nNOS и гиперпродукцией NO, что приводит к NO-индуцированному повреждению нейронов и нарушению центральной регуляции физиологических процессов и нейродегенерации. В миокарде при МС отмечаются изменения экспрессии и локализации nNOS, а также ее функционального взаимодействия с белками цитоскелета, что ведет к нарушениям сокращения миокарда и гипертрофии. В скелетных мышцах nNOS контролирует их сокращение, окислительный метаболизм, вовлечена в регуляцию расслабления сосудов, а также участвует в регуляции глюкозного транспорта. Снижение экспрессии и активности nNOS, а также дизрегуляция ее активности при МС вызывают нарушения этих процессов, вносят существенный вклад в развитие инсулиновой резистентности и ухудшение глюкозного гомеостаза. Таким образом, nNOS может рассматриваться как важная терапевтическая мишень при лечении МС и других метаболических расстройств, а также для предотвращения их осложнений со стороны нервной и сердечно-сосудистой систем и опорно-двигательного аппарата.

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