rmtОбщая реаниматологияGeneral Reanimatology1813-97792411-7110FSBI "SRIGR" RAMS10.15360/1813-9779-2016-2-6-19rmt-1517Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL INVESTIGATIONSДЕЙСТВИЕ АНТИОКСИДАНТА SKQ1 НА СТРУКТУРНОФУНКЦИОНАЛЬНОЕ СОСТОЯНИЕ МОЗГА В ПОСТРЕАНИМАЦИОННОМ ПЕРИОДЕEffect of SkQ1 Antioxidant on Structural and Functional Conditions of The Brain in PostResuscitation PeriodЛоватьМ. Л.LovatM. L.

119192, Москва, ул. Ленинские Горы, д.1, стр. 73;

119992, Москва, ул. Ленинские Горы, д 1, стр. 12

1, Leninskie Gory Str., Build. 73, Moscow 119192;

1, Leninskie Gory Str., Build. 12, Moscow 119991

АврущенкоМ. Ш.AvrushchenkoM. Sh.

107031, Москва, ул. Петровка, д. 25, стр. 2

25, Petrovka Str., Build. 2, Moscow 107031

maria_avr@mail.ruАверинаО. А.AverinaO. A.

119192, Москва, ул. Ленинские Горы, д.1, стр. 73

1, Leninskie Gory Str., Build. 73, Moscow 119192

ПавшинцевВ. В.PavshintsevV. V.

119192, Москва, ул. Ленинские Горы, д.1, стр. 73

1, Leninskie Gory Str., Build. 73, Moscow 119192

ОстроваИ. В.OstrovaI. V.

107031, Москва, ул. Петровка, д. 25, стр. 2

25, Petrovka Str., Build. 2, Moscow 107031

ЗаржецкийЮ. В.ZarzhetskyY. V.

107031, Москва, ул. Петровка, д. 25, стр. 2

25, Petrovka Str., Build. 2, Moscow 107031

МорозВ. В.MorozV. V.

107031, Москва, ул. Петровка, д. 25, стр. 2

25, Petrovka Str., Build. 2, Moscow 107031

ЕгоровМ. В.EgorovM. V.

119192, Москва, ул. Ленинские Горы, д.1, стр. 73

1, Leninskie Gory Str., Build. 73, Moscow 119192

ООО «НИИ Митоинженерии МГУ» Московский государственный университет им. М.В. ЛомоносоваРоссия«Research Institute of Mitoengineering of M. V. Lomonosov Moscow State University» Ltd. M.V. Lomonosov Moscow State UniversityRussian FederationНИИ общей реаниматологии им. В. А. НеговскогоРоссияV. A. Negovsky Institute of General ReanimatologyRussian FederationООО «НИИ Митоинженерии МГУ»Россия«Research Institute of Mitoengineering of M. V. Lomonosov Moscow State University» Ltd.Russian Federation201607072016122619Copyright © Ловать М.Л., Аврущенко М.Ш., Аверина О.А., Павшинцев В.В., Острова И.В., Заржецкий Ю.В., Мороз В.В., Егоров М.В., 20162016Ловать М.Л., Аврущенко М.Ш., Аверина О.А., Павшинцев В.В., Острова И.В., Заржецкий Ю.В., Мороз В.В., Егоров М.В.Lovat M.L., Avrushchenko M.S., Averina O.A., Pavshintsev V.V., Ostrova I.V., Zarzhetsky Y.V., Moroz V.V., Egorov 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.reanimatology.com/rmt/article/view/1517

Цель работы — оценка эффективности митохондриальнонаправленного антиоксиданта SkQ1 для предупреждения постреанимационных нарушений структурнофункционального состояния мозга.

Материалы и методы

Материалы и методы. У 19 половозрелых самцов крыс Вистар вызывали остановку сердца на 7 минут с последующей реанимацией. Часть животных (n=9) получала SkQ1 перорально в дозе 500 нмоль/кг с водой в течение 2х недель (1 неделю до и 1 неделю после реанимации). Контролем служили ложнооперированные животные (n=10). На 4—6е сутки после реанимации у крыс оценивали двигательную активность и тревожность (тест «приподнятый крестообразный лабиринт»), а также сенсомоторную функцию конечностей (тест «сужающаяся дорожка»). Через 7 суток после реанимации на препаратах, окрашенных по Нисслю, определяли плотность нейронов на 1 мм длины их слоя в высокочувствительных к гипоксии нейрональных популяциях (пирамидные нейроны полей СА1 и СА4 гиппокампа, клетки Пуркинье мозжечка). Для выявления возможных механизмов действия SkQ1 проводили иммуногистохимическое исследование экспрессии глиального нейротрофического фактора (GDNF) непрямым пероксидазноантипероксидазным методом с использованием первичных поликлональных антител против GDNF.

Результаты

Результаты. Обнаружено, что ишемияреперфузия приводит к гибели нейронов во всех исследованных отделах мозга, что сопровождается снижением двигательной активности и развитием сенсомоторного дефицита. Применение SkQ1 предупреждает развитие постреанимационных двигательных и сенсомоторных нарушений, существенно уменьшает гибель клеток Пуркинье мозжечка, предотвращает гибель пирамидных нейронов в поле СА4 гиппокампа, но не в поле СА1. Показано, что в популяции клеток Пуркинье мозжечка применение SkQ1 сопровождается увеличением числа GDNFположительных нейронов, более устойчивых к ишемии (переход части GDNFотрицательных клеток в категорию активно экспрессирующих этот фактор нейронов), что способствует их выживанию в постреанимационном периоде.

Заключение

Заключение. Полученные в работе данные свидетельствуют о положительном воздействии SkQ1 на структурнофункциональное состояние мозга в постреанимационном периоде, что обуславливает перспективность применения этого препарата для предотвращения и коррекции постгипоксических энцефалопатий.

The aim was to assess the efficacy of mitochondriatargeted antioxidant SkQ1 in prevention of structural and functional abnormalities of brain postresuscitation after cardiac arrest.

Materials and methods

Materials and methods. Adult male Wistar rats (n=19) underwent cardiac arrest for 7 minutes followed by resuscitation. Nine rats were administered with 500 nmol/kg SkQ1 per os with water for 2 weeks (1 week before and 1 week after resuscitation). A control group consisted of shamoperated animals (n=10). At days 4—6 post operation locomotor activity and anxiety («elevated plus maze» test) and sensorimotor function of limbs («beam walking» test) were examined. Total numbers of neurons per 1 mm of their layer length in vulnerable neuronal populations (cerebellar Purkinje cells and piramidal neurons of hippocampus fields CA1 and CA4) were estimated by histological analysis of the specimens stained with cresyl violet on day 7 postresuscitation. To identify possible mechanisms of SkQ1 action, the immunohistochemical study of a glialderived neurotrophic factor (GDNF) expression in piramidal neurons of hippocampus was performed by indirect peroxidaseantiperoxidase method and antiGDNF primary polyclonal antibodies.

Results

Results. Ischemiareperfusion resulted in neuronal loss in all studied brain areas followed by reduction in locomotor activity and development of sensorimotor deficit. SkQ1 prevented development of postresuscitative locomotor and sensorimotor irregularities, significantly reduced Purkinje cells loss, prevented death of piramidal neurons in hippocampal field CA4, but not in CA1. Data demonstrated, that iIn Purkinje cells from resuscitated rats treated with SkQ1 there was a significant increase in number of GDNFpositive neurons, which were more resistant to ischemia (transition of GDNFnegative cells toward the category of cells actively expressing this factor) that promoted their survival postresuscitation.

Conclusion

Conclusion. Data confirm the positive effects of SkQ1 on structural and functional status of the brain postre suscitation and suggest possible use of SkQ1 for the prevention or correction of posthypoxic encephalopathies.

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