Иммунометаболические нарушения при сахарном диабете 2-го типа, опосредованные активацией инфламмасомы NLRP3, и способы их фармакологической коррекции

Согласно последним исследованиям, хроническое системное воспаление, опосредованное активацией инфламмасомы NOD-подобного рецепторного белка 3 (NLRP3), является одним из ключевых факторов в патофизиологии сахарного диабета (СД) 2-го типа. Основные особенности активации сигнальных каскадов и регуляторных механизмов инфламмасомы NLRP3 при СД 2-го типа (СД2) связаны с тем, что глюкоза, насыщенные жирные кислоты, липотоксичные церамиды, окисленные ЛПНП и холестерин выступают в качестве основных молекулярных паттернов, ассоциированных с повреждением активирующих инфламмасому и запускающих каскад сигнальных механизмов, приводящих к выработке ИЛ-1β и провоспалительных цитокинов. Ряд противодиабетических препаратов не только эффективно контролирует уровень глюкозы, но и корректирует иммунометаболические нарушения, связанные с активацией инфламмасомы NLRP3. Учитывая роль интерлейкина-1β (ИЛ-1β) в воспалении, связанном с СД2, препараты анти-ИЛ-1 терапии, такие как анакинра, канакинумаб, гевокизумаб, исследуются как в экспериментальных моделях СД, так и в клинических испытаниях. Однако применение данной группы ограничивается увеличенным риском инфекционных заболеваний. Среди ингибиторов активации инфламмасомы NLRP3 наиболее исследованными являются MCC950, OLT1177, CY-09, но ни одно из соединений данной группы в настоящее время не применяется в клинической практике. Целью настоящего обзора является оценка роли инфламмасомы NLRP3 в патогенезе СД2, а также потенциала ингибиторов инфламмасомного пути как перспективных средств его терапии.

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