Желчные кислоты

Желчные кислоты, на синтез которых в основном расходуется холестсрол, секретируются из печени в верхний отдел кишечника, где они эмульгируют поступающие с пищей жиры. Выполнив свою функцию, желчные кислоты не выводятся из организма, а большая часть их всасывается в стенки кишечника и поступает в кровь, откуда они захватываются печенью и повторно выделяются в просвет кишечника. Благодаря этому кругообороту желчных кислот потребность печени в холестероле, как правило, ограничена. Мы предположили, что если прервать циркуляцию желчных кислот, то печень будет вынуждена превращать в них холестерол, что должно увеличить потребноегь в холестероле и заставить клетки печени синтезировать больше рецепторов ЛНП.

Класс препаратов, нарушающих кругооборот желчных кислот, был к этому времени уже известен. Речь идет о связывающих желчные кислоты смолах — зернистых полимерах, молекулы которых несут многочисленные положительно заряженные химические группы. При приеме внутрь эти вещества связываются в кишечнике с

желчными кислотами, которые заряжены отрицательно. Смолы не могут всасываться в стенки кишечника и в конечном счете выводятся прочь из организма, унося с собой связанные желчные кислоты. Первое такое соединение, холестирамин, было синтезировано 20 лет назад и оказалось способным в среднем на 10% снижать уровень циркулирующих ЛНП. Анализ данных, накопленных за 10 лет обследования группы мужчин среднего возраста, проведенный недавно в Национальном институте заболеваний сердца, легких и крови, показал, что этого эффекта достаточно, чтобы уменьшить на 20% частоту сердечных приступов. Полученный результат легко объяснить на основе того, что мы знаем теперь о метаболизме ЛНП: нарушение кругооборота желчных кислот приводит к увеличению количества рецепторов ЛНП в клетках печени.

 

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