Эпигенетические механизмы нефропротекции при диабетической нефропатии: в фокусе сиртуин-1

Многочисленными исследованиями показана критическая роль деацетилазы сиртуина-1 (SIRT1) в защите почечных клеток от эндогенных и экзогенных стрессов. Защитная роль SIRT1 была установлена как в подоцитах, так и в клетках почечных канальцев при многих заболеваниях почек, включая диабетическую нефропатию (ДН). Показано также, что SIRT1 оказывает нефропротективные эффекты при ДН отчасти через деацетилирование факторов транскрипции, участвующих в патогенезе заболевания, таких как p53, FOXO, RelA / p65NF-KB, STAT3 и PGC1a / PPARy. Недавно установлено, что специфическая для подоцитов избыточная экспрессия SIRT1 ослабляет протеинурию и повреждение почек на экспериментальной модели ДН, что свидетельствует о возможности использования SIRT1 в качестве потенциальной мишени для лечения заболеваний почек. Кроме того, агонисты SIRT1, такие как ресвера-трол и BF175, уменьшали диабетическое повреждение почек на нескольких экспериментальных моделях животных. Также удалось показать, что пуэрарин, китайское растительное лекарственное средство, активирует SIRT1, обеспечивая нефропротекцию на мышиной модели ДН. Помимо агонистов SIRT1, нефропротективный эффект оказывают и ингибиторы бромодомена, в частности MS417. Эти результаты свидетельствуют о том, что агонисты SIRT1 и ингибиторы бромодомена могут быть новыми потенциальными терапевтическими средствами, замедляющими прогрессирование ДН.

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