Russian Journal of PhysiologyRussian Journal of PhysiologyРоссийский физиологический журнал им. И.М. Сеченова0869-81392658-655XThe Russian Academy of Sciences65173510.31857/S08698139241000105VREWNEEXPERIMENTAL ARTICLESЭКСПЕРИМЕНТАЛЬНЫЕ СТАТЬИResearch ArticleBrain damage in photoinduced ischemia under streptozotocin-induced diabetes in mice with pannexin 1 protein gene knockoutПовреждение мозга при фотоиндуцированной ишемии в условиях стрептозотоцин-индуцированного диабета у мышей с нокаутом гена белка паннексина 1NikolaenkoМ. А.НиколаенкоМ. А.
Russian Federation
gorbi67@mail.ruGulyaevМ. V.ГуляевМ. В.
Russian Federation
gorbi67@mail.ruVolkovaА. А.ВолковаА. А.
Russian Federation
gorbi67@mail.ruGorbachevaL. R.ГорбачеваЛ. Р.
Russian Federation
gorbi67@mail.ruLomonosov Moscow State UniversityМосковский государственный университет имени М. В. ЛомоносоваPirogov Russian National Research Medical UniversityРоссийский национальный исследовательский медицинский университет им. Н. И. Пирогова Минздрава России15102024110101718173202022025Copyright ©; 2024, Russian Academy of SciencesCopyright ©; 2024, Российская академия наук2024Russian Academy of SciencesРоссийская академия наукhttps://journals.eco-vector.com/0869-8139/article/view/651735

Diabetes mellitus (DM), along with ischemia, is one of the top ten causes of death in the globalpopulation, according to the latest World Health Organization (WHO) data. Clinical research data have revealed a high risk of stroke and heart attacks in patients with diabetes. However, there is still a lack of understanding of the involvement of pannexin 1 (Panx1) protein in cerebral ischemia combined with DM. In the presented study, we used the Panx1 gene knockout mice in models of streptozotocin-induced diabetes and photoinduced ischemia to investigate the effect of the Panx1 on the severity of ischemic brain damage and systemic inflammation in mice with a combination of cerebral ischemia and diabetes. It has been found that under conditions of experimental diabetes, the knockout of the Panx1 gene significantly reduces the size of the ischemic lesion, stabilizes the ischemia-induced increase in the blood-brain barrier permeability, reduces the number of errors in the sensorimotor test and the level of neutrophils in the blood. It is important to note that the Panx1 knockout exhibits a protective effect only in the presence of diabetes mellitus, without significantly affecting the severity of ischemic brain injury in mice without streptozotocin-induced diabetes. Panx1 knockout also did not affect the severity of hyperglycemia in animals in this diabetes model. It can be assumed that the efficacy of the treatment for pathologies combined with diabetes mellitus can be enhanced by incorporating pannexin channel blockers into the complex therapy, representing a novel approach to addressing these serious conditions.

Сахарный диабет, наряду с ишемией, входит в десятку патологий, являющихся причиной смертности населения планеты, по последним данным ВОЗ. Данные клинических исследований выявили высокий риск инсульта и инфаркта у пациентов, страдающих диабетом. Вместе с тем в настоящее время нет четкого представления об участии белка паннексина 1 (Panx1) в ишемии мозга на фоне диабета. В представленном исследовании с использованием линии мышей с нокаутом гена Panx1 на моделях стрептозотоцин-вызванного диабета и фотоиндуцированной ишемии было изучено влияние белка Panx1 на выраженность ишемического поражения мозга и системное воспаление у мышей на фоне сочетания ишемии мозга и диабета. Установлено, что в условиях экспериментального диабета нокаут гена Panx1 значимо снижает размер ишемического очага, стабилизирует вызванное ишемией повышение проницаемости гематоэнцефалического барьера, снижает количество ошибок животных в сенсомоторном тесте и уровень нейтрофилов в крови. Важно отметить, что нокаут Panx1 проявляет протекторное действие только на фоне сахарного диабета, не оказывая значимого воздействия на выраженность ишемического поражения мозга у мышей без стрептозотоцин-вызванного диабета. Нокаут гена Panx1 также не влиял на выраженность гипергликемии у животных в этой модели диабета. Можно предположить, что эффективность лечения инсульта в сочетании с сахарным диабетом может быть повышена включением в комплексную терапию блокаторов паннексиновых каналов как нового направления лечения таких тяжелых заболеваний.

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