Нефропротективное действие новых сахароснижающих препаратов: глифлозины

Обзор посвящен рассмотрению нефропротективного действия и его механизмов у новых сахароснижающих препаратов глифлозинов, выявленных в ходе крупномасштабных рандомизированных плацебо-контролируемых испытанийи экспериментальных исследований. Выяснилось, что ингибирование натрий-глюкозного котранспортера 2 (SGLT2) в проксимальных канальцах почек при использовании этих препаратов не только приводит к уменьшению уровня глюкозы в крови, снижению артериального давления, массы тела, содержанию мочевой кислоты в плазме крови, но также задерживает прогрессирование хронической болезни почек, угнетая развитие диабетической нефропатии. Этоблагоприятный эффект является многофакторным. Он обусловлен диуретическим и натрийуретическим действием, уменьшением уровня альбуминурии, ослаблением глюкотоксичности в клетках почечных канальцев, гемодинамическим воздействием на функцию почек и прямым противовоспалительным эффектом. Обсуждается, почему при применении ингибиторов SGLT2 восстанавливается тубулогломерулярная обратная связь, нарушаемая в начальный период диабетической нефропатии и ведущая к гиперфильтрации в оставшихся нефронах. Приводятся сведения о восстановлении нарушенной функции митохондрий благодаря позитивному влиянию препаратов на ионный состав клеток почечных канальцев. Это в значительной степени способствует усилению аутофагии, опосредованного лизосомами пути деградации и удаления поврежденных органелл и нормализующей внутриклеточный гомеостаз. Рассматривается вероятный механизм усиления аутофагии через повышение активности сенсоров энергетической депривации клеток AMPK и SIRT1. Обсуждаются возможные механизмы развития противовоспалительного и антиоксидантного действия ингибиторов SGLT2 через подавление активности инфламмасомы. Рассматривается вопрос о возможном применении глифлозинов при хронической болезни почек, патогенез которой не связан с сахарным диабетом.

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