smjournalСпортивная медицина: наука и практикаSports medicine: research and practice2223-25242587-9014NEICON10.47529/2223-2524.2023.4.8smjournal-539Research ArticleАНТИДОПИНГОВОЕ ОБЕСПЕЧЕНИЕDOPING STUDIESMiR-378a-3p и miR-491-5p как маркеры применения ксеноновых ингаляций в допинг-контроле: пилотное исследованиеMiR-378a-3p and miR-491-5p as markers of xenon abuse in doping controlhttps://orcid.org/0000-0003-3424-0582ПостниковП. В.PostnikovP. V.

Постников Павел Викторович, к.х.н., начальник отдела допингового контроля

105005, Москва, Елизаветинский переулок, 10, стр. 1

Pavel V. Postnikov, Ph.D. (Chemistry), Head of the Doping Control Department

105005, Moscow, Elizavetinskii per., 10-1

drpavelpostnikov@gmail.comhttps://orcid.org/0000-0003-4623-0883ОрджоникидзеЗ. Г.OrdzhonikidzeZ. G.

Орджоникидзе Зураб Гивиевич, д.м.н., заслуженный врач РФ, главный внештатный специалист по спортивной медицине, первый заместитель директора

105120, Москва, ул. Земляной Вал, 53

Zurab G. Ordzhonikidze, M.D., D.Sc. (Medicine), Honored Doctor of the Russian Federation, Chief freelance specialist in sports medicine, First Deputy Director 

105120, Moscow, Zemlyanoy Val str., 53

ozg003@gmail.comhttps://orcid.org/0000-0003-1178-7534ХанферьянР. А.KhanferyanR. A.

Ханферьян Роман Авакович, д.м.н., профессор, Медицинский институт

117198, Москва, ул. Миклухо-Маклая, 6

Roman A. Khanferyan, M.D., D.Sc. (Medicine), professor

117198, Moscow, Miklukho-Maklaya str., 6

khanfer1949@gmail.comhttps://orcid.org/0000-0002-3582-0012ЕфимоваЮ. А.EfimovaYu. A.

Ефимова Юлия Александровна, к.х.н., доцент кафедры аналитической химии им. И.П. Алимарина Института тонких химических технологий им. М.В. Ломоносова 

119571, Москва, Вернадского просп., 86

Yuliya A. Efimova, Ph.D. (Chemistry), Assistant Professor, I.P. Alimarin Department of Analitical Chemistry

119571, Moscow, Vernadskogo prospect, 86

efimova_yulia@bk.ruhttps://orcid.org/0000-0002-0423-7801ПронинаИ. В.ProninaI. V.

Пронина Ирина Валерьевна, к.б.н., главный специалист отдела допингового контроля; старший научный сотрудник лаборатории патогеномики и транскриптомики

Web of Science Research ID G-3951-2014; Scopus Author ID 8161867200

105005, Москва, Елизаветинский переулок, 10, стр. 1; 125315, Москва, Балтийская ул., 8

Irina V. Pronina, Ph.D. (Biology), the main specialist of Doping control Departament; senior scientist of patogenomic and transcriptomic Laboratory

Web of Science Researcher ID G-3951-2014; Scopus Author ID 8161867200

105005, Moscow, Elizavetinskii per., 10–1; 125315, Moscow, Baltiyskaya str., 8

zolly_sten@mail.ruНациональная антидопинговая лаборатория (Институт) Московского государственного университета им. М.В. ЛомоносоваРоссияNational Anti-Doping Laboratory (Institute), Lomonosov Moscow State University (NADL MSU)Russian FederationГАУЗ «Московский научно-практический центр медицинской реабилитации, восстановительной и спортивной медицины Департамента здравоохранения г. Москвы»РоссияState Autonomous Healthcare Institution “Moscow Centre for research and practice in medical rehabilitation, restorative and sports medicine of Moscow healthcare Department”Russian FederationФГАУ ВО «Российский университет дружбы народов»РоссияMedical Institute of People`s Friendship University of Russia (RUDN)Russian FederationФГБОУ «ВО МИРЭА — Российский технологический университет (Институт тонких химических технологий им. М.В. Ломоносова)»РоссияM.V. Lomonosov Institute of Fine Chemical Technologies, MIREA – Russian Technological UniversityRussian FederationНациональная антидопинговая лаборатория (Институт) Московского государственного университета им. М.В. Ломоносова; ФГБУ «Научно-исследовательский институт общей патологии и патофизиологии»РоссияNational Anti-Doping Laboratory (Institute), Lomonosov Moscow State University (NADL MSU); Federal State Budgetary Scientific Institution “Institute of General Pathology and Pathophysiology”Russian Federation2023240320241345464Copyright © Постников П.В., Орджоникидзе З.Г., Ханферьян Р.А., Ефимова Ю.А., Пронина И.В., 20242024Постников П.В., Орджоникидзе З.Г., Ханферьян Р.А., Ефимова Ю.А., Пронина И.В.Postnikov P.V., Ordzhonikidze Z.G., Khanferyan R.A., Efimova Y.A., Pronina I.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.smjournal.ru/jour/article/view/539

Ингаляции ксенона потенциально могут стимулировать синтез в организме эритропоэтина, что привело к запрету на использование этого метода спортсменами Всемирным антидопинговым агентством как в соревновательный, так и внесоревновательный периоды. Определение ксенона в биологических жидкостях, в частности в образцах плазмы крови, затруднено ввиду небольшого окна детектирования. Косвенная детекция агентов, стимулирующих эритропоэз, возможна по изменению некоторых параметров крови при проведении общего клинического анализа, однако данный анализ неспецифичен.

Цель

Цель: поиск новых микроРНК-маркеров, экспрессия которых специфична и значимо изменяется при применении ингаляций ксенона здоровыми добровольцами.

Методы

Методы: количественная полимеразная цепная реакция в реальном времени с использованием прибора CFX96 Bio-Rad с помощью наборов miRCURY® LNA® miRNA SYBR® Green PCR Kit и панелей для исследования профилей экспрессии зрелых микроРНК сигнального пути гипоксии miRCURY LNA™ miRNA Focus Panel.

Результаты

Результаты: установлено, что экспрессия hsa-miR-378а-3p и hsa-miR-491-5p в плазме крови существенно возрастает (более чем в 70 раз) при применении ингаляций ксенона. При этом показатели гематологических параметров до и после подобных ингаляций не показало существенных изменений, что свидетельствует о неэффективности их определения при допинг-контроле для косвенного определения употребления ингаляций ксенона.

Заключение

Заключение: разница в уровнях экспрессии микроРНК до и после использования ксеноновой смеси (Xe/O2 (25:75 v/v)) делает hsa-miR-378а-3p и hsa-miR-491-5p потенциальными претендентами на роль маркеров косвенного определения использования ингаляций ксенона спортсменами.

Xenon stimulates the synthesis of the hormone erythropoietin, which leads to improved oxygen supply to tissues, increased endurance and can be used by athletes to gain an undue advantage in competitions. The World Anti-Doping Agency (WADA) banned its use. The determination of xenon in biological fluids, in particular, in blood plasma samples, is difficult due to the narrow detection window. Its indirect detection is possible by changing in some blood parameters during a clinical analysis (RET%, HGB, HCT, etc.), however, this analysis is nonspecific and the use of other erythropoiesis-stimulating agents can lead to similar changes.

Aims

Aims: The aim of the study was to search for long-term microRNA markers, the expression of which is specific and markedly altered by inhaled xenon.

Methods

Methods: Quantitative real-time PCR was performed on CFX96 Bio-Rad analyser using miRCURY® LNA® miRNA SYBR® Green PCR Kit and panels for studying the expression profiles of mature microRNAs of the hypoxia signaling pathway miRCURY LNA™ miRNA Focus Panel.

Results

Results: Based on statistical data analysis, it was found that the expression of hsa-miR-378a-3p and hsa-miR-491-5p in blood plasma increases significantly (more than 70 times) when xenon inhalations are used as an erythropoiesis stimulator. Measurement of hematological parameters before and after inhalation showed no significant changes that could affect endurance or give competitive advantages.

Conclusion

Conclusion: The evaluated difference in microRNA expression levels before and after administration of the xenon mixture (Xe/O2) makes hsa-miR-378a-3p and hsa-miR-491-5p potential candidates for the role of long-term markers of xenon abuse.

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