gastro-jРоссийский журнал гастроэнтерологии, гепатологии, колопроктологииRussian Journal of Gastroenterology, Hepatology, Coloproctology1382-43762658-6673«Gastro» LLCgastro-j-1230Research ArticleГЕПАТОЛОГИЯHEPATOLOGYЯдерные рецепторы в регуляции транспорта и метаболизма желчных кислотNuclear receptors in regulation of bile acids transport and metabolismШептулинаА. Ф.SheptulinaA. F.ШироковаЕ. Н.ShirokovaYe. N.ИвашкинВ. Т.IvashkinV. T.ГБОУ ВПО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава РФРоссияState educational government-financed institution of higher professional education «Sechenov First Moscow state medical university», Ministry of Healthcare of the Russian FederationRussian Federation2013241020132353245Copyright © Шептулина А.Ф., Широкова Е.Н., Ивашкин В.Т., 20132013Шептулина А.Ф., Широкова Е.Н., Ивашкин В.Т.Sheptulina A.F., Shirokova Y.N., Ivashkin V.T.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.gastro-j.ru/jour/article/view/1230

Цель обзора. Ядерные рецепторы – активируемые лигандами факторы транскрипции, которые участвуют в регуляции метаболизма и транспорта желчных кислот (ЖК) как в физиологических условиях, так и при холестазе. Накопление ЖК и других компонентов желчи в гепатоцитах у пациентов с холестатическими заболеваниями печени сопровождается повреждением печеночных клеток и ведет к развитию фиброза и цирроза печени. Настоящая статья посвящена указанным вопросам.Основные положения. В условиях холестаза происходит активация ряда адаптивных процессов, включающих изменение экспрессии транспортных систем гепатоцитов, уменьшение синтеза ЖК, а также активацию детоксикации и выведения ЖК из печеночных клеток. Все перечисленные механизмы направлены на минимизацию повреждения гепатоцитов, и основную роль в их регуляции играют ядерные рецепторы. Тем не менее, реализация этих адаптивных процессов, по-видимому, является недостаточной для предотвращения развития холестатических заболеваний печени.Заключение. Накопление данных о метаболизме и транспорте ЖК в физиологических условиях и у пациентов с холестатическими заболеваниями печени позволяет не только объяснить механизм действия препаратов, эмпирически применяемых в лечении холестаза уже в течение многих лет, но и создать новые, возможно, более эффективные лекарственные средства. Так, предполагается, что использование лигандов ядерных рецепторов даст возможность усилить механизмы защиты гепатоцитов от повреждения, а, следовательно, замедлить или остановить прогрессирование заболевания.

The aim of review

The aim of review. Nuclear receptors are ligandactivated transcription factors, involved in regulation of metabolism and transport of bile acids (BA) both under physiological, and cholestatic conditions. Accumulation of BA and other bile components in hepatocytes during cholestatic liver diseases is accompanied by liver cells damage and ready to fibrosis and cirrhosis. This article is devoted to the above-mentioned issues.

Key points

Key points. Some adaptive processes including change of hepatocyte transport systems expression reduction of BA synthesis, activation of BA detoxication and elimination are upredgulated during cholestasis. All listed mechanisms are directed to minimize damage hepatocytes and nuclear receptors play the main role in their regulation. Nevertheless, realization of these adaptive processes, apparently, is insufficient to prevent cholestatic liver diseases.

Conclusion

Conclusion. Accumulation of data on metabolism and transport of BA under physiological and cholestatic conditions allows not only to explain the mechanism of action of the drugs empericaly utilized for treatment of cholestasis for many years, but also to develop new, probably, more effective pharmaceuticals. So, it is supposed, that application of nuclear receptor ligands will help to boost hepatocyte protection mechanisms, and, hence, to slow down or arrest progression of disease.

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The authors declare that there are no conflicts of interest present.