arthyperАртериальная гипертензия"Arterial’naya Gipertenziya" ("Arterial Hypertension")1607-419X2411-8524Antihypertensive League10.18705/1607-419X-2008-14-1-44-48arthyper-1172Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESИммунонейтрализация эндогенных ингибиторов Na/K-АТФазы при преэклампсииImmunoneutralization of endogenousNa/K-ATPase inhibitors in preeclampsiaФедороваО.FedorovaO.noemail@neicon.ruРезникВ.ReznikV.noemail@neicon.ruТапильскаяН.TapilskayaN.noemail@neicon.ruКашкинВ.KashkinV.noemail@neicon.ruФроловаЕ.FrolovaE. V.noemail@neicon.ruНикитинаЕ.NikitinaE.noemail@neicon.ruБагровА.BagrovA.noemail@neicon.ruИнститут эволюционной физиологии и биохимии им. И.М. Сеченова РАН, Санкт-Петербург Национальный институт старения, Национальные институты здоровья, Балтимор, США Кафедра акушерства и гинекологии Санкт-Петербургской государственной педиатрической медицинской академии, Санкт-ПетербургRussian Federation2008280220081414448Copyright © Федорова О., Резник В., Тапильская Н., Кашкин В., Фролова Е.V., Никитина Е., Багров А., 20082008Федорова О., Резник В., Тапильская Н., Кашкин В., Фролова Е., Никитина Е., Багров А.Fedorova O., Reznik V., Tapilskaya N., Kashkin V., Frolova E.V., Nikitina E., Bagrov A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://htn.almazovcentre.ru/jour/article/view/1172

Преэклампсия является основной причиной материнской смертности при беременности, но патогенез этого заболевания изучен недостаточно. На основании антигипертензивного действия препарата Digibind (аффинно-очищенных антител к дигоксину) при преэклампсии, была высказана гипотеза о том, что эндогенные дигиталис-подобные ингибиторы Na/K-АТФазы играют роль в патогенезе преэклампсии. Мы предположили, что повышенный уровень эндогенного маринобуфагенина (МБГ), ингибитора Na/K-АТФазы и вазоконстриктора, вызывает угнетение Na/K-АТФазы при преэклампсии. В настоящей работе мы сравнили содержание МБГ в плаценте при преэклампсии и при неосложненной беременности и исследовали иммунологические свойства эндогенного МБГ, выделенного из плацент при преэклампсии методом высокоэффективной жидкостной хроматографии (ВЭЖХ). Уровень концентрации МБГ в плацентах у 6 беременных женщин с преэклампсией (29±2 лет, срок беременности 37±1 недель, артериальное давление 165±9/105±5 мм рт ст.) был в 4 раза выше чем у 8 обследованных с неосложненной беременностью. При ВЭЖХ фракционировании хлороформного экстракта, полученного из плацент беременных женщин с преэклампсией, время элюции эндогенного МБГ было идентично времени элюции МБГ стандарта. Digibind взаимодействовал с хроматографическими фракциями, соответствующими МБГ и другим буфадиенолидам, но не эндогенному оуабаину. Полученные данные свидетельствуют о том, что МБГ является одним из факторов патогенеза преэклампсии и что иммунонейтрализация МБГ может быть одним из подходов к лечению этого заболевания.

Although preeclampsia (PE) is a major cause of maternal and fetal mortality, its pathogenesis is not fully understood. Endogenous digitalis-like cardiotonic steroids (CTS) are implicated in the pathophysiology of PE, as illustrated by clinical observations that Digibind, a digoxin antibody which binds CTS, lowers blood pressure in patients with PE. Recently we reported that plasma levels of marinobufagenin (MBG), a bufadienolide vasoconstrictor CTS, are increased four-fold in patients with severe PE. In the present study, we compared levels of MBG in normal and preeclamptic placentae, and tested whether antibodies against MBG, and against ouabain for their interaction with the material purified from preeclamptic placentae via high-performance liquid chromatography (HPLC). Levels of MBG, but not that of endogenous ouabain, exhibited a four-fold elevation in preeclamptic placentae. The elution time of endogenous placental MBG-like immunoreactive material from reverse-phase HPLC column was identical to that of authentic MBG. Immunoassay based on Digibind did not detect cross-reactivity with HPLC containing ouabain-like immunoreactive material, but cross-reacted with HPLC fractions having retention time similar to that of MBG and other bufadienolides. Our results demonstrate that levels of MBG are significantly elevated in preeclamptic placentae, and suggest that MBG is a potential target for immunoneutralization in patients with preeclampsia.

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