Патогенетическое значение липидов при неалкогольной жировой болезни печени
Аннотация
Цель обзора. Рассмотреть основные представления о повреждающей роли липидов в патогенезе неалкогольной жировой болезни печени (НАЖБП).
Основные положения. По современным представлениям, центральную роль в повреждении клеток печени при НАЖБП играет стресс эндоплазматического ретикулума, который сопровождается дисфункцией белков – шаперонов. Последующие биохимические изменения ведут к нарушению клеточного дыхания, нарушению целостности митохондрий, повышают вероятность гибели гепатоцита. Непосредственным толчком для развития стресса эндоплазматического ретикулума служит избыточное накопление свободных жирных кислот, а индуцируемые ими события в клетке получили название
«липотоксического стресса», «липоапоптоза».
Максимальным повреждающим потенциалом обладают насыщенные жирные кислоты – пальмитиновая и стеариновая, что, возможно, объясняется их более медленным включением в состав эфиров. В патогенезе НАЖБП важную роль играют также другие повреждающие факторы, например окислительный стресс, поэтому сегодня правомерно существование теории «множественных параллельных толчков».
Защитным действием могут обладать ненасыщенные жирные кислоты, эссенциальные фосфолипиды, антиоксиданты, силимарин, гиполипидемические средства, глитазоны. Изучается возможность лечебного применения ингибиторов каспаз, катепсина В, JNK-киназы, «химических шаперонов».
Заключение. Липоапоптоз рассматривается как кардинальный признак НАЖБП, а свободные жирные кислоты – как активаторы программированной гибели гепатоцитов. Дальнейшее изучение молекулярных событий при липотоксическом стрессе, возможно, откроет новую страницу в лечении жировой болезни печени.
Об авторе
Ю. О. Шульпекова
ГБОУ ВПО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Росздрава
Россия
Россия
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Рецензия
Для цитирования:
Шульпекова Ю.О. Патогенетическое значение липидов при неалкогольной жировой болезни печени. Российский журнал гастроэнтерологии, гепатологии, колопроктологии. 2012;22(1):45-56.
For citation:
Shulpekova Yu.O. Pathogenic role of lipids in non-alcoholic fatty liver disease. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2012;22(1):45-56. (In Russ.)
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