mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-PEO-2392mimmun-2392Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESПротективные эффекты препарата нуклеотидной природы “Деринат” на течение и клеточные механизмы черепно-мозговой травмы в экспериментеProtective effects of Derinat, a nucleotide-based drug, on experimental traumatic brain injury, and its cellular mechanismshttps://orcid.org/0000-0002-4999-5913КорневаЕ. А.KornevaE. A.

Корнева Елена Андреевна - доктор медицинских наук, профессор, академик РАН, главный научный сотрудник.

197376, Санкт-Петербург, ул. Акад. Павлова, 12. Тел.: 8 (812) 234-07-24

Korneva Elena A. - PhD, MD (Medicine), Professor, Full Member, RAS, Chief Research Associate.

197376, St. Petersburg, Acad. Pavlov str., 12. Phone: 7 (812) 234-07-24

korneva_helen@mail.ruДмитриенкоЕ. В.DmitrienkoE. V.

Старший лаборант.

СанктПетербург

Senior Laboratory Assistant.

St. Petersburg

МиямураС.MiyamuraS.

Миямура Сюнпэй – студент бакалавриата

Miyamura Shunpei - Undergraduate Student, Graduate

АкимотоН.NodaM.

Акимото Нозоми – доктор наук, научный сотрудник лаборатории патофизиологии

Noda Mami - PhD, Associate Professor, Head, Laboratory of Pathophysiology, Graduate

НодаМ.AkimotoN.

Нода Мами – доктор наук, доцент, заведующая лабораторией патофизиологии

Akimoto Nozomi - PhD, Laboratory Research Assistant, Laboratory of Pathophysiology, Graduate

ФГБНУ Институт экспериментальной медициныРоссияInstitute of Experimental MedicineRussian FederationВысшая школа фармацевтических наук, Университет КюсюЯпонияGraduate School of Pharmaceutical SciencesJapanФГБНУ Институт экспериментальной медициныЯпонияGraduate School of Pharmaceutical SciencesJapan20212112202123613671382Copyright © Корнева Е.А., Дмитриенко Е.В., Миямура С., Акимото Н., Нода М., 20212021Корнева Е.А., Дмитриенко Е.В., Миямура С., Акимото Н., Нода М.Korneva E.A., Dmitrienko E.V., Miyamura S., Noda M., Akimoto N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.mimmun.ru/mimmun/article/view/2392

Черепно-мозговая травма является наиболее частой причиной смерти и инвалидности среди молодых людей, включая спортсменов и солдат, людей в возрасте до 45 лет в промышленно развитых странах, и представляет растущую проблему со здоровьем как в развивающихся странах, так и среди стареющих людей, лечение которых является серьезной проблемой современной медицины. Этот вид травм приводит ко многим видам расстройств и очень часто к инвалидности, что обуславливает необходимость разработки новых методов лечения травм головного мозга. В экспериментах на мышах изучали новый метод лечения травм головного мозга, в частности использовали натриевую соль дезоксирибонуклеиновой кислоты. Этот препарат известен как смесь пептидов с иммуномодулирующим действием, который широко используется для лечения воспалительных, аллергических и аутоаллергических процессов. Натриевая соль дезоксирибонуклеиновой кислоты (DNA) (Деринат), выделенная из икры русского осетра, является препаратом, эффективность применения которого  показана при лечении различных заболеваний. В настоящей работе показаны нейропротекторные, антиоксидантные и противовоспалительные эффекты «Дерината» на модели черепно-мозговой травмы (ЧМТ) у крыс. Внутрибрюшинная инъекция «Дерината» в течение 3 дней после ЧМТ снижает объем повреждения ткани мозга. Иммуногистохимический анализ позволил констатировать морфологические изменения клеток микроглии в коре головного мозга и гиппокампе через 7 дней после ЧМТ, которые значительно снижались при введении препарата, как и индуцированное ЧМТ накопление 8-оксогуанина (8-oxoG) – маркера окислительного повреждения. Для изучения клеточного механизма противовоспалительных эффектов использовали первичную культивированную мышиную микроглию с АТФ (50 мкм и 1 мм) в качестве вещества, высвобождающегося в месте повреждения, для имитации воспалительной реакции in vitro. Введение «Дерината» обуславливало повышение количества мРНК нейротрофического фактора глиальных клеток (GDNF) и фактора роста нервов (NGF) в присутствии АТФ, а уровень мРНК активатора тканевого плазминогена (tPA) снижался при действии АТФ в сочетании с «Деринатом» или без него. Хотя экспрессия мРНК интерлейкина-6 (IL6) не изменялась при действии АТФ, она возрастала при аппликации «Дерината». Те же показатели фактора-α некроза опухоли (TNFα) были значительно ингибированы. Комплекс полученных данных раскрывает механизмы иммуномодулирующего действия дезоксирибонуклеиновых кислот при ЧМТ.

Traumatic brain injury is the most common cause of death and disability in young people including sport athletes and soldiers, people under 45 years of age in the industrialized countries, representing a growing health problem in developing countries, as well as in aging communities. Treatment of the latter is a serious challenge for modern medicine. This type of injury leads to many kinds of disorders and, quite often, to disability. These issue require development of new methods for brain trauma treatment. The new approach to brain trauma treatment was studied in murine experiments. In particular, sodium salt of deoxyribonucleic acid (DNA) was used. This preparation is a drug known as a mixture of peptides with immunomodulatory effect which is widely used for different kinds of therapy. Derinat, a sodium salt of DNA, isolated from the caviar of Russian sturgeon, is a proven immunomodulator for treatment of diseases associatd with reactive oxygen species (ROS), including brain ischemia-reperfusion (IR) injury. Here we show that treatment with Derinat exert neuroprotective, anti-oxidative, and anti-inflammatory effects in experimental model of traumatic brain injury (TBI) in rats. Intraperitoneal injection of Derinat several times over 3 days after TBI showed less pronounced damage of the injured brain area. Immunohistochemical study showed that the Derinat-induced morphological changes of microglia in cerebral cortex and hippocampus 7 days after TBI. TBI-induced accumulation of 8-oxoguanine (8-oxoG), the marker of oxidative damage, was significantly attenuated by Derinat administration, both on 7th and 14th day after TBI. To investigate cellular mechanism of anti-inflammatory effects, the primary cultures of murine microglia supplied with ATP (50 M and 1 mM), as a substance released at injured site, were used to mimic the in vitro inflammatory response. Derinate treatment caused an increase of glial levels of mRNAs encoding neurotrophic factor (GDNF) and nerve growth factor (NGF) in the presence of ATP, whereas tissue plasminogen activator (tPA) mRNA was inhibited by ATP with or without Derinat. Interleukin-6 (IL-6) mRNA expression was not affected by ATP but was increased by Derinat. Both mRNA and protein levels of ATP-induced TNFα production were significantly inhibited by Derinat. These results partially contribute to understanding mechanisms of immunomodulatory effects of DNA preparations in traumatic brain injury.

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