Современные представления о патогенезе гастроэзофагеальной рефлюксной болезни

В основе развития гастроэзофагеальной рефлюксной болезни лежит нарушение моторики гастроэзофагеальной зоны и появление воспалительных изменений в слизистой оболочке дистального отдела пищевода. Целью нашего обзора явилось предоставление обсуждения механизмов, приводящих к ее развитию. Проведен литературный поиск публикаций в базах данных eLibrary.Ru, PubMed. Рассматривались и рецензировались статьи, и опубликованные после 2000 года. После применения критериев отбора в окончательный список литературы было включено 80 статей. Считалось, что рефлюкс-эзофагит начинается, когда рефлюксная кислота и пепсин повреждают эпителий пищевода, повышая его проницаемость, что позволяет соляной кислоте и пепсину проникать вглубь эпителиального покрова и атаковать интактные клетки. Показано, что механизмы повреждения эпителия пищевода, вызванные кислотным и желчным рефлюксом разные. Так, кислотный рефлюкс вызывает повреждение тканей путем денатурации белков, разрушения их протеазами, активации циклооксигеназы-2 (ЦОГ-2), c-myc и митоген-активируемой протеинкиназы, ограничивает скорость синтеза простагландинов. Воздействие желчных кислот обуславливает цитотоксические механизмы, активацию протоонкогена и c-myc, способствующих эпигеномному механизму канцерогенеза. Изменение микробиома пищевода индуцирует активацию врожденного и адаптивного звена иммунной системы, а также сенсорной нервной системы. Иммунокомпетентные клетки экспрессируют рецепторы для многочисленных трансмиттеров, высвобождаемых из сенсорных и вегетативных нервов, что позволяет нервной системе напрямую регулировать функциональную активность иммунной системы. Клетки иммунной системы также могут вырабатывать нейротрансмиттеры и регулировать в свою очередь работу нервной системы, в том числе и клеток пейсмекеров, приводя к развитию рефлюкса, воздействию на слизистую пищевода или соляной кислоты с пепсином, или желчных кислот, вызывающих воспаление и замыкающих порочный круг.

патогенез гастроэзофагеальной рефлюксной болезни, соляная кислота, желчные кислоты, цитокины, микробиом, иммунная система, сенсорная нервная система

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