medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/ms2023-136medsovet-7558Research ArticleЗАБОЛЕВАНИЯ БИЛИАРНОЙ СИСТЕМЫ И ПЕЧЕНИDISEASES OF THE BILIARY SYSTEM AND LIVERУрсодезоксихолевая кислота: уникальные свойства и клиническое применениеUrsodeoxycholic acid: unique properties and clinical applicationshttps://orcid.org/0000-0001-8913-140XМаевскаяМ. В.MaevskayM. V.

Маевская Марина Викторовна, д.м.н., профессор 

119991, Москва, ул. Трубецкая, д. 8, стр. 2

Marina V. Maevskaya, Dr. Sci. (Med.), Professor 

8, Bldg. 2, Trubetskaya St., Moscow, 119991

mvmaevskaya@me.comПервый Московский государственный медицинский университет имени И.М. Сеченова (Сеченовский Университет)РоссияSechenov First Moscow State Medical University (Sechenov University)Russian Federation2023250520230896105Copyright © Маевская М.В., 20232023Маевская М.В.Maevskay M.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-sovet.pro/jour/article/view/7558

Урсодезоксихолевая кислота (УДХК) – природная гидрофильная желчная кислота, которая у человека присутствует в виде незначительной доли от общего количества желчных кислот (5%). Ее уникальные свойства лежат в основе применения при ряде заболеваний печени в качестве терапии первой линии. Способность УДХК снижать секрецию холестерина в желчь, образовывать смешанные мицеллы (жидкие кристаллы) с молекулами холестерина и взаимодействовать с многофункциональными ядерными рецепторами активно используется в лечении и профилактике желчнокаменной болезни. УДХК обладает способностью стимулировать гепатобилиарную секрецию, способствует секреции холангиоцитами бикарбоната, что актуально для пациентов с  первичным билиарным холангитом  (ПБХ) и  первичным склерозирующим холангитом  (ПСХ). УДХК активирует белки-транспортеры, такие как экспортная помпа желчных кислот (BSEP), протеин мультирезистентности 2 (MRP2) – переносчик конъюгатов, анионный обменник 2-го типа (AE2), и способствует их перемещению к каналикулярной мембране клеток. УДХК действует как плейотропный агент, играющий уникальную роль в модуляции классического митохондриального пути апоптоза в различных типах клеток. Двойные молекулярные связи УДХК служат ловушкой для свободных радикалов, что подавляет процессы перекисного окисления липидов. Способность УДХК встраиваться в  мембраны митохондрий приводит к подавлению активности митохондриальных оксидазных ферментов, ответственных за продукцию супероксид-аниона. УДХК активирует аутофагию и  способствует выведению токсичных жирных кислот из  гепатоцитов, уменьшая стеатоз печени, оказывает противовоспалительное и антифибротическое действие. Описаны ее иммуномодулирующий и  антиканцерогенный эффекты. УДХК включена в  международные и  российские клинические рекомендации по лечению пациентов с различными формами заболеваний печени (ПБХ, ПСХ, внутрипеченочный холестаз беременных, лекарственный холестаз, алкогольная болезнь печени с холестатическим компонентом), желчнокаменной болезнью, муковисцидозом. В фармакотерапии неалкогольной жировой болезни печени УДХК является единственным препаратом, который обладает двунаправленным действием на печень и кардиометаболические риски. 

Ursodeoxycholic acid (UDCA) is a natural hydrophilic bile acid, which is present in humans as a small fraction of the total amount of bile acids (5%). Its unique properties underlie its use in a number of liver diseases as a first-line therapy. The ability of UDCA to reduce the secretion of cholesterol into bile, form mixed micelles (liquid crystals) with cholesterol molecules and interact with multifunctional nuclear receptors, are actively used in the treatment and prevention of cholelithiasis. UDCA has the ability to stimulate hepatobiliary secretion, promotes the secretion of bicarbonate by cholangiocytes, which is relevant for patients with primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). UDCA activates transporter proteins such as bile acid export pump (BSEP), multiresistance protein 2 (MRP2) – conjugates transporter, type 2 anion exchanger (AE2), and promotes their movement to the canalicular membrane of cells. UDCA acts as a pleiotropic agent that plays a unique role in modulating the classical mitochondrial pathway of apoptosis in various cell types. Double molecular bonds of UDCA serve as a trap for free radicals, which suppresses the processes of lipid peroxidation. The ability of UDCA to penetrate into mitochondrial membranes leads to suppression of the activity of mitochondrial oxidase enzymes responsible for the production of superoxide anion. UDCA activates autophagy and promotes the elimination of toxic fatty acids from hepatocytes, reducing liver steatosis, UDCA has anti-inflammatory, antifibrotic, immunomodulatory and anticarcinogenic effects. UDCA is included in international and Russian clinical guidelines for the treatment of patients with various liver diseases (PBC, PSC, intrahepatic cholestasis of pregnancy, drug-induced cholestasis, alcoholic liver disease with cholestatic component), cholelithiasis, cystic fibrosis. In the pharmacotherapy of non-alcoholic fatty liver disease, UDCA is the only drug that has a bi-directional effect on the liver and cardiovascular system.

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