cardiotomskСибирский журнал клинической и экспериментальной медициныSiberian Journal of Clinical and Experimental Medicine2713-29272713-265XTSU publishing10.29001/2073-8552-2023-38-4-29-39cardiotomsk-2048Research ArticleОБЗОРЫ И ЛЕКЦИИREVIEWS AND LECTURESАпелин – пептид, повышающий устойчивость органов и клеток к ишемии и реперфузии. Молекулярный механизм (обзор)Apelin is a peptide increasing tolerance of organs and cells to ischemia and reperfusion. The molecular mechanism (the review)https://orcid.org/0000-0002-1607-1482ПоповС. B.PopovS. V.

Попов Сергей Валентинович, д-р мед. наук, профессор, академик РАН, директор Научно-исследовательского института кардиологии

634012, Томск, ул. Киевская, 111а

Sergey V. Popov, Dr. Sci. (Med.), Academician of the Russian Academy of Sciences, Director of the Cardiology Research Institute

111A, Kyevskaya str., Tomsk, 634012

press@cardio-tomsk.ruhttps://orcid.org/0000-0003-2264-1928НарыжнаяН. В.NaryzhnayaN. V.

Нарыжная Наталья Владимировна, д-р мед. наук, ведущий научный сотрудник, лаборатория экспериментальной кардиологии

634012, Томск, ул. Киевская, 111а

Natalia V. Naryzhnaya, Dr. Sci. (Med.), Leading Research Scientist, Laboratory of Experimental Cardiology

111A, Kyevskaya str., Tomsk, 634012

natalynar@yandex.ruhttps://orcid.org/0000-0002-4502-0836СиротинаМ. А.SirotinaM. A.

Сиротина Мария Александровна, младший научный сотрудник, лаборатория экспериментальной кардиологии

634012, Томск, ул. Киевская, 111а

Maria A. Sirotina, Junior Research Scientist, Laboratory of Experimental Cardiology

111A, Kyevskaya str., Tomsk, 634012

sirotina_maria@mail.ruhttps://orcid.org/0000-0002-6020-1598МасловЛ. Н.MaslovL. N.

Маслов Леонид Николаевич, д-р мед. наук, профессор, заведующий лабораторией экспериментальной кардиологии

634012, Томск, ул. Киевская, 111а

Leonid N. Maslov, Dr. Sci. (Med.), Professor, Head of the Laboratory of Experimental Cardiology

111A, Kyevskaya str., Tomsk, 634012

Maslov@cardio-tomsk.ruhttps://orcid.org/0000-0003-1808-556XМухомедзяновА. В.MukhomedzyanovA. V.

Мухомедзянов Александр Валерьевич, канд. мед. наук, научный сотрудник, лаборатория экспериментальной кардиологии

634012, Томск, ул. Киевская, 111а

Alexander V. Mukhomedzyanov, Cand. Sci. (Med.), Research Scientist

111A, Kyevskaya str., Tomsk, 634012

sasha_m91@mail.ruhttps://orcid.org/0000-0001-9603-822XКурбатовБ. К.KurbatovB. K.

Курбатов Борис Константинович, младший научный сотрудник, лаборатория экспериментальной кардиологии

634012, Томск, ул. Киевская, 111а

Boris K. Kurbatov, Junior Research Scientist, Laboratory of Experimental Cardiology

111A, Kyevskaya str., Tomsk, 634012

bobersanker@gmail.comhttps://orcid.org/0000-0002-5890-071XГорбуновА. С.GorbunovA. S.

Горбунов Александр Сергеевич, канд. мед. наук, старший научный сотрудник, лаборатория экспериментальной кардиологии

634012, Томск, ул. Киевская, 111а

Alexsandr S. Gorbunov, Cand. Sci. (Med), Senior Research Scientist, Laboratory of Experimental Cardiology

111A, Kyevskaya str., Tomsk, 634012

shura.gorbunov.1982@mail.ruhttps://orcid.org/0000-0002-4300-5763КилинМ.KilinM.

Килин Михаил, лаборант, лаборатория экспериментальной кардиологии

634012, Томск, ул. Киевская, 111а

Mikhail Kilin, Laboratory Assistant, Laboratory of Experimental Cardiology

111A, Kyevskaya str., Tomsk, 634012

Kilin112233@gmail.comhttps://orcid.org/0000-0003-4341-3844КрылатовА. В.KrylatovA. V.

Крылатов Андрей Владимирович, канд. мед. наук, лаборант-исследователь, лаборатория экспериментальной кардиологии

634012, Томск, ул. Киевская, 111а

Andrey V. Krylatov, Cand. Sci. (Med), Research Assistant, Laboratory of Experimental Cardiology

111A, Kyevskaya str., Tomsk, 634012

krylatovav@mail.ruhttps://orcid.org/0000-0002-8939-2340ПодоксеновЮ. К.PodeksenovYu. K.

Подоксенов Юрий Кириллович, д-р мед. наук, ведущий научный сотрудник, отделение анестезиологии-реанимации

634012, Томск, ул. Киевская, 111а

Yury K. Podoksenov, Dr. Sci. (Med.), Leading Research Scientist, Department of Cardiovascular Surgery

111A, Kyevskaya str., Tomsk, 634012

uk@cardio-tomsk.ruhttps://orcid.org/0000-0003-3275-4811АзевВ. Н.AzevV. N.

Азев Вячеслав Николаевич, канд. хим. наук, старший научный сотрудник, руководитель Группы химии пептидов, отдел биотехнологии

634012, Томск, ул. Киевская, 111а

Viatcheslav N. Azev, Dr. Sci. (Chem.), Senior Research Scientist, Head of the Group of Peptide Chemistry, Department of biotechnology

6, Nauki avenue, Pushchino, 142290, Moscow Region

viatcheslav.azev@bibch.ruhttps://orcid.org/0000-0003-1291-0661СуфиановаГ. З.SufianovaG. Z.

Суфианова Галина Зиновьевна, д-р мед. наук, профессор, заведующий кафедрой фармакологии

625023, Тюмень, ул. Одесская, 54

Maria S. Khlеstkina, Assistant Professor, Department of Pharmacology

54, Odessa str., Tyumen, 625023

sufarm@mail.ruhttps://orcid.org/0000-0002-5966-8916ХлесткинаМ. С.KhlestkinaM. S.

Хлесткина Мария Сергеевна, ассистент кафедры фармакологии

625023, Тюмень, ул. Одесская, 54

Maria S. Khlеstkina, Assistant Professor, Department of Pharmacology

54, Odessa str., Tyumen, 625023

kh_m_s@mail.ruНаучно-исследовательский институт кардиологии, Томский национальный исследовательский медицинский центр Российской академии наукРоссияCardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of SciencesRussian FederationФилиал Института биоорганической химии имени Шемякина Овчинникова Российской академии наукРоссияBranch of Shemyakin Ovchinnikov Institute of Bioorganic Chemistry, the Russian Academy of SciencesRussian FederationТюменский государственный медицинский университет Министерства здравоохранения Российской ФедерацииРоссияTyumen State Medical UniversityRussian Federation2023301220233842939Copyright © Попов С.B., Нарыжная Н.В., Сиротина М.А., Маслов Л.Н., Мухомедзянов А.В., Курбатов Б.К., Горбунов А.С., Килин М., Крылатов А.В., Подоксенов Ю.К., Азев В.Н., Суфианова Г.З., Хлесткина М.С., 20232023Попов С.B., Нарыжная Н.В., Сиротина М.А., Маслов Л.Н., Мухомедзянов А.В., Курбатов Б.К., Горбунов А.С., Килин М., Крылатов А.В., Подоксенов Ю.К., Азев В.Н., Суфианова Г.З., Хлесткина М.С.Popov S.V., Naryzhnaya N.V., Sirotina M.A., Maslov L.N., Mukhomedzyanov A.V., Kurbatov B.K., Gorbunov A.S., Kilin M., Krylatov A.V., Podeksenov Y.K., Azev V.N., Sufianova G.Z., Khlestkina M.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.sibjcem.ru/jour/article/view/2048

Ишемические-реперфузионные повреждения органов лежат в основе таких распространенных патологий, как ишемический инсульт и инфаркт миокарда и являются причиной смертности и инвалидизации населения. Кроме того, ишемическое повреждение легких наблюдается при тромбоэмболии легочной артерии. Успехи трансплантологии, как и широкое применение аортокоронарного шунтирования, ставят проблему ишемии и реперфузии органов при этих манипуляциях. Прогресс, достигнутый в прошедшие три десятилетия в отношении лечения инсульта и острого инфаркта миокарда (ОИМ), в последние годы замедлился. Поскольку пациенты с инсультом, ОИМ, ишемическим повреждением почки или легкого поступают в стационар после развития патологии, воздействовать на его формирование уже невозможно. Однако возможно повлиять на реперфузионное повреждение органов. Значительный прогресс в повышении эффективности трансплантации почек, в лечении инсульта, эмболии легочных артерий и ОИМ может быть достигнут за счет разработки новых препаратов, способных с высокой эффективностью предотвращать реперфузионное повреждение органов. Прототипами препаратов подобного действия могут стать синтетические аналоги апелина с длительным периодом полувыведения. Было обнаружено, что апелины могут повышать толерантность сердца, головного мозга, почек и легких к ишемии/реперфузии (И/Р). Апелины ингибируют апоптоз и активируют аутофагию кардиомиоцитов. Нейропротекторное, кардиопротекторное, ренопротекторное и пульмонопротекторное действие апелинов реализуется через внутриклеточный сигналлинг, включающий протеинкиназы, митохондриальную пору переменной проницаемости и АТФ-чувствительные К+-каналы. Устойчивые к воздействию ферментов аналоги апелина являются перспективными пептидами для лечения ОИМ, инсульта и И/Р повреждений легких и почек.

Ischemic-reperfusion injuries of organs underlie such common pathologies as ischemic stroke and myocardial infarction and are the cause of death and disability in the population. In addition, ischemic lung damage is observed in pulmonary embolism. Advances in transplantology, as well as the widespread use of coronary artery bypass grafting, raise the problem of ischemia and reperfusion of organs during these manipulations. Progress made over the past three decades in the treatment of stroke and acute myocardial infarction (AMI) has slowed in recent years. Since patients with stroke and AMI are admitted to the hospital with ischemic damage to the brain or heart, it is no longer possible to influence its formation. However, it is possible to affect reperfusion injury to organs. Significant progress in improving the efficiency of kidney transplantation, in the treatment of stroke, pulmonary embolism and AMI can be achieved through the development of new drugs that can effectively prevent reperfusion damage of organs. Synthetic analogues of apelin with a long half-life can become prototypes of drugs with similar action. It has been found that apelins can increase the tolerance of the heart, brain, kidneys and lungs to ischemia/reperfusion (I/R). Apelins inhibit apoptosis and activate cardiomyocyte autophagy. The neuroprotective, cardioprotective, renoprotective, and pulmonoprotective effects of apelins are realized through intracellular signaling, including protein kinases, a mitochondrial variable permeability pore, and ATP-sensitive K+ channels. Enzyme-resistant analogues of apelin are promising peptides for the treatment of AMI, stroke, and I/R damage to the lungs, and kidneys.

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