Патогенез нарушений моторной функции толстой кишки при функциональном запоре

Цель обзора: представить современные данные о ведущих звеньях патогенеза функционального запора.

Основные положения. Запор встречается у 15 % взрослого населения в мире и приводит к значимому снижению качества жизни, а в сочетании с некоторыми другими симптомами может свидетельствовать о наличии органической патологии желудочно-кишечного тракта. Патогенетической основой функционального запора (ФЗ) с медленным кишечным транзитом является снижение моторной функции толстой кишки, которое подтверждается результатами манометрии высокого разрешения. ФЗ характеризуется нарушениями таких моторных паттернов толстой кишки, как низко- и высокоамплитудные пропульсивные сокращения, сегментарные непропульсивные сокращения и общее повышение давления. Основные механизмы ФЗ, связанные с нейрогенной дисрегуляцией, включают нарушение функции серого и белого вещества головного мозга, а также повышение тонуса симпатической нервной системы при сопутствующем уменьшении влияний холинергических нервов, иннервирующих толстую кишку. Значимая роль в развитии ФЗ принадлежит уменьшению пула интерстициальных клеток, играющих роль кишечного водителя ритма, вследствие нарушения процесса их самообновления. Сопутствующие ФЗ изменения в энтеральной нервной системе включают относительное превышение вклада тормозных влияний и уменьшение активности холинэргических и серотонинэргических нейронов, стимулирующих кишечную моторику. Определенное значение в возникновении сниженной моторной функции толстой кишки может иметь дисбаланс выработки кишечных гормонов, синтезируемых энтероэндокринными клетками, а именно, дефицит стимуляторов моторики, к которым относятся мотилин, гастрин, грелин и холецистокинин, а также относительный избыток гормонов, подавляющих моторику (соматостатин и вазоактивный интестинальный полипептид). Изменения состава кишечной микробиоты также могут способствовать возникновению ФЗ, что связано с нарушением профиля метаболитов, продуцируемых кишечными бактериями.

Заключение. ФЗ представляет собой классическое мультифакториальное заболевание, в этиологии которого неблагоприятные влияния генотипа сочетаются с множественными приобретенными факторами риска. Более полное понимание молекулярных механизмов развития ФЗ может послужить основой для появления новых эффективных методов лечения этого распространенного заболевания.

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