vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/vjgb-24-34vavilov-4143Research ArticleРЕПРОДУКТИВНЫЕ ТЕХНОЛОГИИPHYSIOLOGICAL GENETICSМетаболомный профиль мочи крыс с артериальной гипертонией разного генезаUrine metabolic profile in rats with arterial hypertension of different genesisСорокоумоваА. А.SorokoumovaA. A.

Новосибирск

Novosibirsk

evanesalisa@yandex.ruСеряпинаА. А.SeryapinaA. A.

Новосибирск

Novosibirsk

seryapina@bionet.nsc.ruПолитыкоЮ. К.PolitykoYu. K.

Новосибирск

Novosibirsk

ЯньшолеЛ. В.YansholeL. V.

Новосибирск

Novosibirsk

ЦенталовичЮ. П.TsentalovichYu. P.

Новосибирск

Novosibirsk

ГилинскийМ. А.GilinskyМ. А.

Новосибирск

Novosibirsk

МаркельА. Л.MarkelА. L.

Новосибирск

Novosibirsk

Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наукРоссияInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of SciencesRussian FederationФедеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук; Научно-исследовательский институт нейронаук и медициныРоссияInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Scientific Research Institute of Neurosciences and MedicineRussian FederationИнститут «Международный томографический центр» Сибирского отделения Российской академии наукРоссияInternational Tomography Center of the Siberian Branch of the Russian Academy of SciencesRussian FederationНаучно-исследовательский институт нейронаук и медициныРоссияScientific Research Institute of Neurosciences and MedicineRussian FederationФедеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук; Новосибирский национальный исследовательский государственный университетРоссияInstitute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences; Novosibirsk State UniversityRussian Federation202430052024283299307Copyright © Сорокоумова А.А., Серяпина А.А., Политыко Ю.К., Яньшоле Л.В., Центалович Ю.П., Гилинский М.А., Маркель А.Л., 20242024Сорокоумова А.А., Серяпина А.А., Политыко Ю.К., Яньшоле Л.В., Центалович Ю.П., Гилинский М.А., Маркель А.Л.Sorokoumova A.A., Seryapina A.A., Polityko Y.K., Yanshole L.V., Tsentalovich Y.P., Gilinsky М.А., Markel А.L.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/4143

Многообразие патогенетических механизмов, лежащих в основе артериальной гипертонии, приводит к необходимости разработки персонализированного подхода к диагностике и терапии заболевания. Одним из перспективных методов для персонализированной медицины является метаболомика, которая позволяет получить комплексное представление о физиологических процессах, происходящих в организме. Метаболом – это совокупность низкомолекулярных веществ, определяемых в образце и являющихся промежуточными и конечными продуктами метаболизма клеток. Изменения в содержании и соотношении метаболитов в исследуемом образце маркируют соответствующие патогенетические механизмы, выделяя их, что особенно важно для такого мультифакторного заболевания, как артериальная гипертония. Для идентификации метаболомных маркеров гипертензивных состояний разного генеза были исследованы три разные формы артериальной гипертонии (АГ): крысы c наследственной АГ (линия крыс НИСАГ/ISIAH); крысы с АГ, индуцированной введением L-NAME (модель эндотелиальной дисфункции с нарушением продукции NO); крысы с АГ, вызванной введением дезоксикортикостерона в сочетании с солевой нагрузкой (гормон-зависимая форма – DOCA-солевая АГ). В качестве нормотензивного контроля были использованы крысы линии WAG. У всех животных собрали образцы суточной мочи, метаболомный профиль которой проанализировали методом количественной ЯМР-спектроскопии. Затем с помощью методов многомерной статистики выявили потенциальные метаболомные маркеры исследуемых форм гипертензивных состояний. Анализ полученных данных показал, что для наследственной стресс-индуцированной артериальной гипертонии у крыс линии НИСАГ характерно снижение содержания следующих метаболитов в моче: никотинамида и 1-метилникотинамида (маркеры воспалительных процессов), N-ацетилглутамата (цикл оксида азота), изобутирата и метилацетоацетата (микробиота кишечника). Фармакологически индуцированные формы АГ (группы L-NAME и DOCA+NaCl) не имеют общих с наследственной АГ метаболомных маркеров. Их отличают один общий маркер, N,N-диметилглицин, и два специфических – холин (для группы L-NAME) и 1-метилникотинамид (для группы крыс с DOCA-солевой артериальной гипертонией).

The diversity of pathogenetic mechanisms underlying arterial hypertension leads to the necessity to devise a personalized approach to the diagnosis and treatment of the disease. Metabolomics is one of the promising methods for personalized medicine, as it provides a comprehensive understanding of the physiological processes occurring in the body. The metabolome is a set of low-molecular substances available for detection in a sample and representing intermediate and final products of cell metabolism. Changes in the content and ratio of metabolites in the sample mark the corresponding pathogenetic mechanisms by highlighting them, which is especially important for such a multifactorial disease as arterial hypertension. To identify metabolomic markers for hypertensive conditions of different origins, three forms of arterial hypertension (AH) were studied: rats with hereditary AH (ISIAH rat strain); rats with AH induced by L-NAME administration (a model of endothelial dysfunction with impaired NO production); rats with AH caused by the administration of deoxycorticosterone in combination with salt loading (hormone-dependent form – DOCAsalt AH). WAG rats were used as normotensive controls. 24-hour urine samples were collected from all animals and analyzed by quantitative NMR spectroscopy for metabolic profiling. Then, potential metabolomic markers for the studied forms of hypertensive conditions were identified using multivariate statistics. Analysis of the data obtained showed that hereditary stress-induced arterial hypertension in ISIAH rats was characterized by a decrease in the following urine metabolites: nicotinamide and 1-methylnicotinamide (markers of inflammatory processes), N- ace tyl glutamate (nitric oxide cycle), isobutyrate and methyl acetoacetate (gut microbiota). Pharmacologically induced forms of hypertension (the L-NAME and DOCA+NaCl groups) do not share metabolomic markers with hereditary AH. They are differentiated by N,N-dimethylglycine (both groups), choline (the L-NAME group) and 1-methylnicotinamide (the group of rats with DOCA-salt hypertension).

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