Связывание радиоактивного ЛНП с мембранами

В совместных исследованиях с П. Кованен мы вводили собакам связывающую желчные кислоты смолу отдельно и в сочетании с ингибиторами фермента. Через 2 недели животным делали биопсию печени и оценивали в полученном материале количество рецепторов ЛНП, определяя связывание радиоактивного ЛНП с мембранами. Как и ожидалось, после введения одной только смолы отмечалось умеренное увеличение числа рецепторов ЛНП в печени, а после введения смолы вместе с ингибитором гидроксиметил- глутарил-КоА—редуктазы их становилось существенно больше. На уровне всего организма в целом это проявлялось в том, что скорость удаления ЛНП из циркуляции значительно повышалась и их концентрация уменьшалась на 75%. Мы продолжили эту работу в сотрудничестве с Д. Билхейме- ром и С. Гранди. Больным гетерозиготной формой семейной гиперхоле- стеролемии вводили смолу и мевинолин, и концентрация циркулирующих ЛНП у них снижалась на 50%, приближаясь к нормальному уровню. Опыты с радиоактивными ЛНП показали, что такой эффект был обусловлен именно увеличением количества рецепторов ЛНП, т.е. нам действительно удалось заставить единственный полноценный ген рецепторов ЛНП работать вдвое эффективнее и продуцировать такое количество рецепторов, которое могло обеспечить нормальную скорость удаления ЛНП из кровяного русла.

Применение описанной комбинации веществ не дает эффекта в случае гомозиготной формы семейной гиперхоле- стеролемин, поскольку у больных ею

нет ни одного нормального гена рецепторов ЛНП. Чтобы помочь нм, следует искать другие пути. Интересный хирургический подход был осуществлен Т. Старзлом из Медицинской школы Питтсбургского университета. Основан он на том предположении, что в отсутствие рецепторов ЛНП при гомозиготном варианте заболевания можно добиться частичной коррекции, если больному пересадить печень от нормального донора. Старзл пересадил печень ребенка, погибшего в результате несчастного случая, шест плетней девочке, страдавшей тяжелой формой гомозиготной семейной гиперхолестеро- лемии. (К моменту операции больная перенесла уже несколько сердечных приступов, и ее сердце было так ослаблено, что требовалась его трансплантация.)



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