Внутриклеточные сигнальные пути при диабетической нефропатии: новые мишени для нефропротекции


И.А. Бондарь, В.В. Климонтов

Кафедра эндокринологии Новосибирского государственного медицинского университета, Новосибирск
Диабетическая нефропатия (ДН) – одно из наиболее тяжелых осложнений сахарного диабета (СД), ведущая причина терминальной почечной недостаточности в индустриально развитых странах. Высокая концентрация глюкозы является основным фактором, запускающим каскад метаболических нарушений в клетках клубочков и канальцев почек при СД. Влияние гипергликемии на нефроциты усугубляют продукты гликирования, ангиотензин II, трансформирующий фактор роста β, фактор роста соединительной ткани, фактор роста эндотелия сосудов, моноцитарный хемоаттрактантный протеин-1 и другие факторы роста. Действие этих факторов реализуется через внутриклеточные молекулярные взаимодействия (сигнальные пути), важнейшими из которых являются протеинкиназа С и митоген-активируемые киназы, цитоплазматические белки Smad, Янус-киназа, передатчики сигнала и активаторы транскрипции STAT, регулятор трансляции mTOR, ядерные рецепторы PPARα и PPARγ. Активация данных сигнальных путей определяет основные патофизиологические процессы в почках при ДН: глюкозотоксичность, окислительный стресс, хроническое воспаление низкой интенсивности, фиброгенез. Направленное воздействие на внутриклеточные механизмы передачи сигнала является новым подходом к нефропротекции при ДН. Перспективы в лечении ДН связаны, в частности, с ингибированием протеинкиназы С (рубоксистаурин), сигнального пути Smad (GW788388 и др.), сигнального пути Янус-киназа/STAT (супрессоры цитокинового сигнала SOCS1 и SOCS3, статины), mTOR (сиролимус), а также с использованием агонистов PPARα (фибраты) и PPARγ (тиазолидиндионы).

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Об авторах / Для корреспонденции


Бондарь И.А. – профессор, заведующая кафедрой эндокринологии Новосибирского государственного медицинского университета, д.м.н.
Климонтов В.В. – доцент кафедры эндокринологии Новосибирского государственного медицинского университета, д.м.н.
Факс: (383) 315-98-63, 346-27-00, e-mail: klimontov@mail.ru


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