Современные фармакологические подходы к лечению первичного нефротического синдрома

Обзор посвящен рассмотрению наиболее распространенных лекарственных средств, применяемых в настоящее время в процессе лечения первичного нефротического синдрома. Проанализированы механизмы фармакологической активности глюкокортикостероидов, АКТГ, ингибиторов кальциневрина циклоспорина А и такролимуса, алкилирующих соединений циклофосфамида и хлорамбуцила, микофенолата мофетила, левамизола, абатацепта, ритуксимаба и ряда других, недавно созданных моноклональных АТ. Предпринята попытка выделить иммунные и неиммунные механизмы действия наиболее распространенных препаратов, касающиеся как воздействия на звенья иммуногенеза отмеченных заболеваний, так и прямого влияния на подоциты, обеспечивающие проницаемость клубочкового фильтрационного барьера и развитие протеинурии. Иммунные механизмы действия кортикостероидов обусловлены взаимодействием с глюкокортикоидными рецепторами лимфоцитов, а неиммунные – со стимулированием этих же рецепторов в подоцитах. Выяснено, что активация АКТГ меланокортиновых рецепторов вносит вклад в благоприятный эффект препарата при нефротическом синдроме. Обсуждается, что иммунный механизм ингибиторов кальциневрина обеспечивается подавлением тканевого и гуморального иммунитета, а неиммунный в значительной степени обусловлен сохранением активности таких белков подоцитов, как синаптоподин и кофилин. Приведены доказательства, убеждающие, что благоприятный эффект ритуксимаба при гломерулопатиях связан с взаимодействием препарата с белком SMPDL-3b в лимфоцитах и подоцитах. Рассматриваются механизмы действия микофенолата мофетила, ингибирующего активность фермента инозин 5-монофосфатдегидрогеназы, что обусловливает подавление синтеза гуанозиновых нуклеотидов как в лимфоцитах, так и в клетках клубочкового мезангиума. Подчеркнуто, что действие левамизола при нефротическом синдроме, вероятно, связано с нормализацией соотношения цитокинов, вырабатываемых различными Т-хелперами, а также c увеличением экспрессии и активности глюкокортикоидных рецепторов. Рассмотрены механизмы фармакологической активности ряда моноклональных АТ, а также галактозы, благоприятный эффект которой, возможно, обеспечивается связыванием с предполагаемым фактором проницаемости, вырабатываемым лимфоцитами.

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