Russian Journal of PhysiologyRussian Journal of PhysiologyРоссийский физиологический журнал им. И.М. Сеченова0869-81392658-655XThe Russian Academy of Sciences65156810.31857/S0869813923050114XRSONBEXPERIMENTAL ARTICLESЭКСПЕРИМЕНТАЛЬНЫЕ СТАТЬИRecovery of the Functional Activity of KATP-Channels of Pial Arteries after Ischemia/Reperfusion Using Cell TherapyВосстановление функциональной активности КАТФ-каналов пиальных артерий после ишемии/реперфузии с помощью клеточной терапииSokolovaI. B.СоколоваИ. Б.SokolovaIB@infran.ruGorshkovaO. P.ГоршковаО. П.SokolovaIB@infran.ruPavlov Institute of Physiology, Russian Academy of SciencesИнститут физиологии им. И.П. Павлова РАН01052023109562964201022025Copyright ©; 2023, И.Б. Соколова, О.П. ГоршковаCopyright ©; 2023, И.Б. Соколова, О.П. Горшкова2023И.Б. Соколова, О.П. ГоршковаИ.Б. Соколова, О.П. Горшковаhttps://journals.eco-vector.com/0869-8139/article/view/651568

This study aims to examine the efficiency of intravenous transplantation of human mesenchymal stem cells (hMSCs) performed 7 days after cerebral ischemia/reperfusion (I/R) for recovery of the functional activity of KATP-channels of cerebral arteries. Using a device for intravital visualization of pial vessels, the reaction of arteries to the KATP-channel blocker glibenclamide (GB), the activator of the same channels of pinacidil (PI), acetylcholine (ACh), and ACh against a background of GB action (ACh/GB) 14 and 21 days after I/R and intravenous hMSC transplantation performed 7 days after ischemic exposure. On exposure to GB 14 days after I/R, 1.5–1.8 times fewer arteries narrowed than in the sham–operated (SO) rats. By day 21 after I/R, the constriction reaction was completely restored, except for arteries with a diameter more 40 μm. In the cell–therapy group, the constrictor response to GB was completely recovered to the level of SO animals in arteries with a diameter less than 40 μm by 14 day after I/R exposure; in arteries with a diameter of more than 40 μm, the constriction reaction did not recover until 21 days. The number of dilations per ACh/GB compared to a clear ACh in SO rats was reduced in 1.6–1.8 times on 14 day after I/R and in 1.6–6.6 after 21 days. In I/R animals on 14 day, the number of dilatations per ACh/GB compared to clear ACh was significantly increased in arteries with a diameter of more than 20 μm by 1.5–1.7 times, and after 21 days in arteries with a diameter of more than 40 μm by 1.2 times. After the introduction of hMSC, GB blocked ACh–mediated dilation in arteries less than 40 μm in diameter both on days 14 and 21 after I/R. In arteries with a diameter of more than 40 μm the functional activity of KATP-channels did not recover until 21 days. Conclusion. I/R of the rat cerebral cortex reduces the contribution of KATP-channels to maintaining the basal tone of the pial arteries and almost completely excludes these channels from the formation of ACh–mediated dilation during 21 days of the postischemic period. Practically did not participate in the dilatory response. Intravenous transplantation of hMSC, performed 7 days after I/R, results in restoration of participation of SMC KATP-channels in maintaining the basal tone and ACh–mediated dilatation of pial arteries with a diameter less than 40 μm already 14 days after I/R.

Цель работы – выяснить эффективность внутривенной трансплантации мезенхимных стволовых клеток человека (МСКч), проведенной на 7-е сут после ишемии/реперфузии (И/Р) головного мозга, для восстановления функциональной активности КАТФ-каналов церебральных артерий. С помощью установки для прижизненной визуализации пиальных сосудов исследовали реакцию артерий на воздействие блокатора КАТФ-каналов глибенкламида (GB), активатора этих же каналов пинацидила (PI), ацетилхолина (ACh), и AСh на фоне действия GB (ACh/GB) через 14 и 21 сут после И/Р головного мозга (12-минутная окклюзия обеих сонных артерий с управляемой гипотензией) и внутривенной трансплантации МСКч, проведенной на 7-е сут после ишемического воздействия. Установлено, что на 14-е сут после И/Р число сузившихся артерий на GB уменьшилось в 1.5–1.8 раза по сравнению с ложнооперированными крысами. К 21-м сут после И/Р констрикторная реакция полностью восстановилась кроме артерий диаметром более 40 мкм. В группе клеточной терапии констрикторная реакция на GB была полностью восстановлена до уровня ложнооперированных крыс у артерий диаметром менее 40 мкм уже к 14-м сут после И/Р; у более крупных сосудов не восстановилась до 21-х сут. Число дилатаций на ACh/GB по сравнению с чистым AСh у ложнооперированных крыс понижено в 1.6–1.8 раза на 14-е сут и в 1.6–6.6 раза на 21-е сут. У И/Р животных на 14-е сут число дилатаций на ACh/GB по сравнению с чистым AСh статистически значимо повышено у артерий диаметром более 20 мкм в 1.5–1.7 раза, а через 21 сут у артерий диаметром более 40 мкм в 1.2 раза. После введения МСКч GB блокировал AСh-опосредованную дилатацию у артерий диаметром менее 40 мкм и на 14-е, и на 21-е сут после И/Р. У сосудов диаметром более 40 мкм функциональная активность КАТФ-каналов не восстановилась до 21 сут. Делается заключение, что И/Р коры головного мозга крыс снижает вклад КАТФ-каналов в поддержание базального тонуса пиальных артерий и практически полностью выключает данные каналы из формирования AСh-опосредованной дилатации на протяжении 21 сут постишемического периода. Внутривенная трансплантация МСКч, проведенная на 7-е сут после И/Р, приводит к восстановлению участия КАТФ-каналов гладкомышечных клеток в поддержании базального тонуса и осуществлении AСh-опосредованной дилатации пиальных артерий диаметром менее 40 мкм уже через 14 сут после перенесенной И/Р.

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