Российская академия наук


ROLE OF THE ATP-DEPENDENT POTASSIUM CHANNELS AND NITRIC OXIDE SYSTEM IN NEUROPROTECTIVE EFFECT OF PRECONDITIONING



страница245/848
Дата10.12.2019
Размер1.98 Mb.
1   ...   241   242   243   244   245   246   247   248   ...   848
ROLE OF THE ATP-DEPENDENT POTASSIUM CHANNELS AND NITRIC OXIDE SYSTEM IN NEUROPROTECTIVE EFFECT OF PRECONDITIONING

Deryagin O.G.1, Gavrilova S.A.1, Golubeva A.V.1, Andrianov V.V.2,3, Yafarova G.G.2, Gainutdinov Kh.L.2,3, Koshelev V.B.1

1Faculty of Fundamental Medicine, Lomonosov Moscow State University, Moscow, Russia; 2Kazan Physical-Technical Institute of Russian Academy of Sciences, Kazan, Republic of Tatarstan, Russia; 3Institute of Fundamental Medicine and Biology of Kazan Federal University, Kazan, Republic of Tatarstan, Russia; olegderyagin@gmail.com
This study aimed to investigate the role of ATP-dependent potassium (K+ATP) channels in realization of neuroprotective effect of the ischemic and pharmacological types of preconditioning (IP and PhP), and the relationship between K+ATP-channels and nitric oxide (NO) system in rats with experimental ischemic stroke.

Stroke was modeled in male rats (n = 140) by electrocoagulation of the middle cerebral artery branch (MCAO). The nonselective K+ATP-channel blocker glibenclamide and K+ATP-channel opener diazoxide were used. IP and PhP were performed one day before MCAO: IP - by alternately clamping of the right and left common carotid arteries, and PhP – by intraventricular administration of the diazoxide solution. The concentrations of NO and its metabolites (NO3- and NO2-) were assessed at 5, 9, 24, 72 hours after MCAO.

IP reduced the lesion area by 37% (p<0.05). A similar effect was observed with the diazoxide PhP. Pretreatment with glibenclamide abolished the effect of IP, indicating a key role of the K+ATP-channels in

neuroprotective effect of preconditioning. On the third day the NO levels in brain tissue of rats pretreated with glibenclamide were increased by 65% (p = 0.0005), that may be due to activation of the inducible NO-synthase of microglial cells in response to K+ATP-channel blockade. However earlier, at the 24-hour timepoint blockade of K+ATP-channels led to decrease in NO3- and NO2- serum levels (p < 0.03). A possible explanation for this is the inclusion of NO in free-radical reactions within the microglial activation zone, preventing its oxidation to the final products.

It is assumed that during the delayed phase of preconditioning, mitochondria pass into the low-energy state, reducing the oxygen consumption and facilitating its diffusion from the capillaries to distant cells. K+ATP-channel activation by diazoxide reduced the NO content in cerebral cortex after 9 and 72 hours following MCAO (p=0.037 and p=0.002, respectively). We refer this result to the reduced NO-synthase activity in preconditioned mitochondria.

The present study revealed a relationship between the K+ATP-channel state and the NO (and its metabolites) level dynamics in rats with experimental ischemic stroke, that requires a further investigation of these subtle interactions.



Каталог: news
news -> Умеренные когнитивные нарушения у больных с сосудистым поражением головного мозга 14. 01. 11 нервные болезни
news -> 15-й международный медицинский форум «качество и безопасность оказания медицинской помощи» нижегородская ярмарка россия, Нижний Новгород
news -> Сборник материалов
news -> Разработка технологии вкусоароматических добавок с применением сенсорных технологий
news -> «казұму 85 жыл: жетістіктері мен келешегі» халықаралық ғылыми-тəжірибелік конференция аясындағы «клиникалық фармация: халықаралық ТƏжірибе мен қазақстанның денсаулық сақтаудағы даму ерекшеліктері»
news -> Программа международной научно-практической конференции 14-15 апреля 2016 г. Курск 2016
news -> Российская академия наук отделение физиологических наук


Поделитесь с Вашими друзьями:
1   ...   241   242   243   244   245   246   247   248   ...   848


База данных защищена авторским правом ©zodorov.ru 2017
обратиться к администрации

    Главная страница