pmedpharmФармация и фармакологияPharmacy & Pharmacology2307-92662413-2241Pyatigorsk Medical and Pharmaceutical Institute - branch of Volgograd State Medical Univer10.19163/2307-9266-2024-12-3-219-230pmedpharm-1611Research ArticleОРИГИНАЛЬНАЯ СТАТЬЯRESEARCH ARTICLEАнализ эффективности действия митохондриально-направленного антиоксиданта SkQ1 на модели ишемии и реперфузии миокарда крыс. Акцент на морфологическом и ультраструктурном исследовании тканиAnalysis of mitochondrial-targeted antioxidant SkQ1 effectiveness on myocardial ischemia-reperfusion injury in a rat model: Focus on morphological and ultrastructural tissue studyhttps://orcid.org/0000-0002-9430-937XСенокосоваЕ. А.SenokosovaE. A.

кандидат биологических наук, заведующий лабораторией клеточных технологий ФГБНУ НИИ КПССЗ.

650002, Россия, г. Кемерово, Сосновый б-р, д. 6

Candidate of Sciences (Biology), Head of Laboratory of Cell Technologies, Laboratory of Cell Technologies, Research Institute for Complex Issues of Cardiovascular Diseases. 

6 Barbarash Blvd., Kemerovo, Russia, 650002

sergeewa.ew@yandex.ruhttps://orcid.org/0000-0002-1079-1956ВеликановаЕ. А.VelikanovaE. A.

кандидат биологических наук, научный сотрудник лаборатории клеточных технологий НИИ КПССЗ.

650002, Россия, г. Кемерово, Сосновый б-р, д. 6

Candidate of Sciences (Biology), researcher of Laboratory of Cell Technologies, Research Institute for Complex Issues of Cardiovascular Diseases. 

6 Barbarash Blvd., Kemerovo, Russia, 650002

veliea@kemcardio.ruhttps://orcid.org/0000-0002-5558-3229МухамадияровР. А.MukhamadiyarovR. A.

кандидат биологических наук, старший научный сотрудник лаборатории молекулярной, трансляционной и цифровой медицины ФГБНУ НИИ КПССЗ.

650002, Россия, г. Кемерово, Сосновый б-р, д. 6

Candidate of Sciences (Biology), senior researcher of Laboratory of Molecular, Translation and Digital Medicine, Research Institute for Complex Issues of Cardiovascular Diseases. 

6 Barbarash Blvd., Kemerovo, Russia, 650002

muhara@kemcardio.ruhttps://orcid.org/0000-0003-2731-6294СидороваО. Д.SidorovaO. D.

кандидат медицинских наук, преподаватель, доцент ГБПОУ «КМК». 

650991, Россия, г. Кемерово, ул. Николая Островского, д. 10.

Candidate of Sciences (Medicine), lecturer, associate professor of Kuzbass Medical College. 

10 N. Ostrovskiy Str., Kemerovo, Russia, 650991

sod-0204@yandex.ruhttps://orcid.org/0000-0002-2500-2147КривкинаЕ. О.KrivkinaE. O.

младший научный сотрудник лаборатории клеточных технологий ФГБНУ НИИ КПССЗ. 

650002, Россия, г. Кемерово, Сосновый б-р, д. 6

junior researcher of Laboratory of Cell Technologies, Research Institute for Complex Issues of Cardiovascular Diseases. 

6 Barbarash Blvd., Kemerovo, Russia, 650002

kriveo@kemcardio.ruhttps://orcid.org/0000-0002-8874-0788АнтоноваЛ. В.AntonovaL. V.

доктор медицинских наук, ведущий научный сотрудник лаборатории клеточных технологий ФГБНУ НИИ КПССЗ.

650002, Россия, г. Кемерово, Сосновый б-р, д. 6

Doctor of Sciences (Medicine), leading researcher of Research Institute for Complex Issues of Cardiovascular Diseases.

6 Barbarash Blvd., Kemerovo, Russia, 650002

antolv@kemcardio.ruhttps://orcid.org/0000-0001-8370-3083ГригорьевЕ. В.GrigorievE. V.

доктор медицинских наук, заместитель директора по научной и лечебной работе ФГБНУ НИИ КПССЗ; профессор РАН. 

650002, Россия, г. Кемерово, Сосновый б-р, д. 6

Doctor of Sciences (Medicine), Deputy Director for Scientific and Medical Work of Research Institute for Complex Issues of Cardiovascular Diseases; professor RAS. 

6 Barbarash Blvd., Kemerovo, Russia, 650002

grigev@kemcardio.ruФедеральное государственное бюджетное научное учреждение «Научно-исследовательский институт комплексных проблем сердечно-сосудистых заболеваний».РоссияResearch Institute for Complex Issues of Cardiovascular DiseasesRussian FederationФедеральное государственное бюджетное научное учреждение «Научно-исследовательский институт комплексных проблем сердечно-сосудистых заболеваний»РоссияResearch Institute for Complex Issues of Cardiovascular DiseasesRussian FederationГосударственное бюджетное профессиональное образовательное учреждение «Кузбасский медицинский колледж».РоссияKuzbass Medical CollegeRussian Federation202411032025123219230Copyright © Сенокосова Е.А., Великанова Е.А., Мухамадияров Р.А., Сидорова О.Д., Кривкина Е.О., Антонова Л.В., Григорьев Е.В., 20252025Сенокосова Е.А., Великанова Е.А., Мухамадияров Р.А., Сидорова О.Д., Кривкина Е.О., Антонова Л.В., Григорьев Е.В.Senokosova E.A., Velikanova E.A., Mukhamadiyarov R.A., Sidorova O.D., Krivkina E.O., Antonova L.V., Grigoriev E.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.pharmpharm.ru/jour/article/view/1611

Митохондриально-направленный антиоксидант SkQ1 демонстрирует высокую эффективность на разных экспериментальных моделях и может занять важное место в минимизации постоперационных осложнений при проведении операций на открытом сердце в условиях искусственного кровообращения или консервации трансплантата.

Цель

Цель. Оценить степень сохранности и изменений изолированного сердца крысы, которое подверглось длительной кардиоплегической ишемии, при условии донации разных концентраций SkQ1.

Материалы и методы

Материалы и методы. Исследование эффективности SkQ1 (12 нг/мл, 120 нг/мл и контрольная группа – без донации SkQ1) проведено на модели изолированного сердца крыс линии Wistar (n=15) по Лангендорфу. Провели биохимический анализ (супероксиддисмутазы 2 [СОД-2], малонового диальдегида [МДА] тропонин-I, сердечного белка, связывающего жирные кислоты [с-БСЖК]), гистологию ткани (окраска гематоксилин-эозином), сканирующую электронную микроскопию в обратно-рассеянных электронах и иммунофлуоресцентную окраску на цитохром С и редуктазу цитохрома Р-450. Количественные данные обрабатывали в программе GraphPad Prism 7 (GraphPad Software, США).

Результаты

Результаты. Наибольшая сохранность ткани миокарда выявлена при поддержке SkQ1 в концентрации 12 нг/мл: наименьшие концентрации МДА (49,5 [41,1; 58,9] мкмоль/г), тропонин-I (22,3 [20,3; 23,9] пг/мл), с-БСЖК (0,8 [0,6; 16,0] нг/мл) логично сочетались с обширными зонами с сохранением поперечной исчерченности, умеренным интерстициальным отёком. Также выявлены недеформированые митохондрии, расположенные между сократительными волокнами, иммунофлуоресценция цитохрома С была распределена локально, интенсивность свечения на 40% выше в сравнении с контролем (р <0,0001). Увеличение концентрации SkQ1 до 120 нг/мл скорее способствовало усугублению окислительного стресcа: концентрации МДА (63,8 [62,5; 83,0] мкмоль/г) и c-БСЖК (12,8 [4,1; 15,3] нг/мл) была ближе к контрольным значениям. Миокард данной группы охарактеризован резко выраженным отёком, фрагментацией мышечных волокон, некоторые группы кардиомиоцитов находились в состоянии глыбчатого распада, миоцитолиза и внутриклеточного отёка. Цитохром С был распределён равномерно в цитозоле кардиомиоцитов.

Заключение

Заключение. SkQ1 в концентрации 12 нг/мл проявлял выраженные антиоксидантные свойства в отношении ишемизированного миокарда, что позволило получить более высокую степень сохранности сердечной мышцы в сравнении с применением SkQ1 в концентрация 120 нг/мл, которая усугубила окислительный стресс и структурные изменения ткани.

Mitochondrial-targeted antioxidant SkQ1 demonstrates a high efficiency in animal models and potentially can be used for minimizing postoperative complications in an on-pump open-heart surgery.

The aim of study was to the assessment of preservation degree and changes in the isolated rat heart characterized by prolonged cardioplegic ischemia, under the condition of donation of different SkQ1concentrations.

Material and methods

Material and methods. Isolated Langendorff-perfused rat hearts of Wistar line (n=15) were included in the presented study; the effectiveness of 12 ng/mL and 120 ng/mL of SkQ1 was analyzed. A biochemical analysis (superoxide dismutase 2 [SOD2], malondialdehyde [MDA], Troponin-I, heart-type fatty acid-binding protein [H-FABP]), a histological analysis of tissues (hematoxylin and eosin staining), scanning electron microscopy using backscattered electrons and immunofluorescence staining for cytochrome C and cytochrome P450 reductase were performed. The quantitative data were processed using GraphPad Prism 7 (Graph Pad Software, USA).

Results

Results. The optimal myocardial preservation was discovered while using 12 ng/mL of SkQ1: the lowest concentrations of MDA (49.5 [41.1; 58.9] mmol/g), Troponin-I (22.3 [20.3; 23.9] pg/mL) and H-FABP (0.8 [0.6; 16.0] ng/mL) were associated with extensive areas of tissues with preserved transverse dark and light bands and a moderate interstitial edema. Moreover, non-deformed mitochondria were located mainly between the contractile fibers. Cytochrome C immunofluorescence was distributed locally, the luminescence intensity was 40% higher compared to the control group (p <0.0001). Increasing SkQ1 concentration to 120 ng/mL contributed to the aggravation of oxidative stress: MDA (63.8 [62.5; 83.0] mmol/g) and H-FABP (12.8 [4.1; 15.3] ng/mL) concentrations were closer to the control group values. Myocardial tissue in this group was characterized by a pronounced edema and a fragmentation of muscle fibers. There were signs of cardiomyocyte decay, myocytolysis and an intracellular edema. Cytochrome C was distributed evenly.

Conclusion

Conclusion. 12 ng/mL of SkQ1 demonstrates pronounced antioxidant effects in the ischemic myocardium leading to a higher degree preservation of the heart muscle compared to 120 ng/mL of SkQ1 that was associated with an aggravated oxidative stress and structural changes of the tissue.

пластомитинSkQ1изолированное сердце крысыокислительный стрессишемия-репефузияперфузия по Лангендорфугистологиясканирующая электронная микроскопияиммунофлуоресценцияplastomitinSkQ1isolated rat heartoxidative stressischemia-reperfusion injuryLangendorff perfusionhistologyscanning electron microscopyimmunofluorescenceРабота выполнена при поддержке комплексной программы фундаментальных научных исследований СО РАН в рамках фундаментальной темы НИИ КПССЗ № 0419-2022-0001 «Молекулярные, клеточные и биомеханические механизмы патогенеза сердечно-сосудистых заболеваний в разработке новых методов лечения заболеваний сердечно-сосудистой системы на основе персонифицированной фармакотерапии, внедрения малоинвазивных медицинских изделий, биоматериалов и тканеинженерных имплантатов».This research was supported by the Complex Program of Fundamental Research of the Siberian Branch of the Russian Academy of Sciences within the framework of the fundamental research project of the Research Institute for Complex Issues of Cardiovascular Diseases No. 0419-2022-0001.ReferencesSoeur J., Eilstein J., Lereaux G., Jones C., Marrot L. 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The authors declare that there are no conflicts of interest present.