pmedpharmФармация и фармакологияPharmacy & Pharmacology2307-92662413-2241Pyatigorsk Medical and Pharmaceutical Institute - branch of Volgograd State Medical Univer10.19163/2307-9266-2022-10-1-104-112pmedpharm-1030Research ArticleФАРМАКОЛОГИЯ И КЛИНИЧЕСКАЯ ФАРМАКОЛОГИЯPHARMACOLOGY AND CLINICAL PHARMACOLOGYОЦЕНКА ПЕРСПЕКТИВНОСТИ ИНГИБИРОВАНИЯ ABCB1-БЕЛКА В ГЕМАТОЭНЦЕФАЛИЧЕСКОМ БАРЬЕРЕ КАК МЕТОДА ПОВЫШЕНИЯ ЭФФЕКТИВНОСТИ ФАРМАКОТЕРАПИИ ЦЕРЕБРАЛЬНОЙ ИШЕМИИEVALUATION OF ABCB1-PROTEIN INHIBITION PROSPECTIVENESS IN HEMATOENCEPHALIC BARRIER AS METHOD FOR INCREASING EFFICIENCY OF PHARMACOTHERAPY IN CEREBRAL ISCHEMIAhttps://orcid.org/0000-0002-5618-7607ЧерныхИ. В.ChernykhI. V.

кандидат биологических наук, доцент, заведующий кафедрой фармацевтической химии

390026, Россия, г. Рязань, ул. Высоковольтная, д. 9

Candidate of Sciences (Biology), Associate Professor, Head of the Department of Pharmaceutical Chemistry

9, Vysokovoltnaya St., Ryazan, Russia, 390026

ivchernykh88@mail.ruhttps://orcid.org/0000-0003-1688-0017ЩулькинА. В.ShchulkinA. V.

доктор медицинских наук, доцент, профессор кафедры фармакологии с курсом фармации ФДПО

390026, Россия, г. Рязань, ул. Высоковольтная, д. 9

Doctor of Sciences (Medicine), Associate Professor, Professor of the Department of Pharmacology with the Course of Pharmacy

9, Vysokovoltnaya St., Ryazan, Russia, 390026

alekseyshulkin@rambler.ruhttps://orcid.org/0000-0002-1116-6271ГацаногаМ. В.GatsanogaM. V.

кандидат медицинских наук, ассистент кафедры фармакологии с курсом фармации ФДПО

390026, Россия, г. Рязань, ул. Высоковольтная, д. 9

Candidate of Sciences (Medicine), Assistant of the Department of Pharmacology with the Course of Pharmacy

9, Vysokovoltnaya St., Ryazan, Russia, 390026

mvgatsanoga@mail.ruhttps://orcid.org/0000-0001-6887-4888ЯкушеваЕ. Н.YakushevaE. N.

доктор медицинских наук, профессор, заведующая кафедрой фармакологии с курсом фармации ФДПО

390026, Россия, г. Рязань, ул. Высоковольтная, д. 9

Doctor of Sciences (Medicine), Professor, Head of the Department of Pharmacology with a Course in Pharmacy

9, Vysokovoltnaya St., Ryazan, Russia, 390026

e.yakusheva@rzgmu.ruФедеральное государственное бюджетное образовательное учреждение высшего образования «Рязанский государственный медицинский университет имени академика И.П. Павлова» Министерства здравоохранения Российской ФедерацииРоссияRyazan State Medical University named after academician I.P. PavlovRussian Federation202206032022101104112Copyright © Черных И.В., Щулькин А.В., Гацанога М.В., Якушева Е.Н., 20222022Черных И.В., Щулькин А.В., Гацанога М.В., Якушева Е.Н.Chernykh I.V., Shchulkin A.V., Gatsanoga M.V., Yakusheva E.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.pharmpharm.ru/jour/article/view/1030Цель

Цель. Оценка ингибирования ABCB1-белка в гематоэнцефалическом барьере с целью повышения эффективности нейропротекторной терапии фокальной и глобальной церебральной ишемии.

Материалы и методы

Материалы и методы. Работа выполнена на 103 крысах-самцах линии Вистар. На 1-й группе (n=33) анализировали нейропротекторную активность субстрата ABCB1-белка – нимодипина (0,4 мг/кг) по снижению площади некроза головного мозга после 1-часовой окклюзии средней мозговой артерии с 24-часовой реперфузией (фокальная ишемия). На 2-й группе (n=60) эффективность нимодипина анализировали по снижению летальности крыс и уровня неврологического дефицита (НД) на фоне билатеральной окклюзии общих сонных артерий (глобальная ишемия). В обеих группах нимодипин использовался отдельно или в сочетании с ингибитором ABCB1-белка – омепразолом (17,6 мг/кг). Препараты вводились внутривенно.

Результаты

Результаты. Введение нимодипина 1-й группе привело к сокращению очага некроза на 28% по сравнению с серией контроля. Омепразол не вызвал изменения площади некроза. Комбинация препаратов вызвала снижение площади некроза по отношению к контролю на 29%, в сравнении с серией нимодипина различий не было. Нимодипин сокращал летальность крыс 2-й группы на фоне патологии (тенденция). Омепразол не изменял летальность. Комбинация препаратов снижала летальность по сравнению с сериями контроля и нимодипина. Введение омепразола не сокращало балл неврологического дефицита относительно контроля. В серии нимодипина НД был ниже контроля через 24 ч. на 88%. При введении комбинации препаратов данный показатель снижался по отношению к контролю через 4, 12, 24, 48 и 72 ч. на 88%, 80%, 88%, 87% и 86%, а по отношению к серии нимодипина через 4 и 48 ч − на 60% и 67%.

Заключение

Заключение. Ингибирование ABCB1-белка является перспективным для повышения эффективности нейропротекторной терапии глобальной ишемии, но не фокальной ишемии мозга.

The aim of the article is to evaluate the ABCB1 protein inhibition in the blood-brain barrier to increase the effectiveness of neuroprotective therapy for focal and global cerebral ischemia.

Materials and methods

Materials and methods. The work was performed on 103 male Wistar rats. In the 1st group (n=33), the neuroprotective activity of the ABCB1 protein substrate, nimodipine (0.4 mg/kg), was analyzed in terms of reducing the area of the brain necrosis after a 1-hour occlusion of the middle cerebral artery with a 24-hour reperfusion (focal ischemia). In the 2nd group (n=60), the effectiveness of nimodipine was analyzed by reducing the lethality of rats and the neurological deficit (ND) level against the background of the bilateral occlusion of the common carotid arteries (global ischemia). In both groups, nimodipine was used alone or in the combination with omeprazole, the ABCB1 protein inhibitor (17.6 mg/kg). The drugs were administered intravenously.

Results

Results. The nimodipine administration to the 1st group led to the reduction of the necrosis focus by 28% compared with the control series. Omeprazole did not cause a change in the area of the necrosis. The combination of drugs caused a decrease in the area of the necrosis in relation to the control by 29%; there were no differences in comparison with the nimodipine series. Nimodipine reduced the rats’ lethality in the 2nd group against the background of the pathology (a tendency). Omeprazole alone did not change the mortality. The drug combination reduced the mortality compared to the control and nimodipine series. The administration of omeprazole alone did not reduce the neurological deficit score relative to the control. In the nimodipine series, ND was 88% lower than the control, after 24 hours. With the administration of the drugs combination, this indicator decreased in relation to the control by 88%, 80%, 88%, 87% and 86% after 4, 12, 24, 48 and 72 hours, respectively, and in relation to the nimodipine series it decreased by 60% and 67% after 4 and 48 hours.

Conclusion

Conclusion. The ABCB1 protein inhibition is promising for increasing the effectiveness of neuroprotective therapy for global ischemia, but not for focal cerebral ischemia.

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