vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/VJGB-23-64vavilov-3862Research ArticleМОДЕЛИРОВАНИЕ ПАТОЛОГИЙMODELING OF DISORDERSМетаболомный профиль сыворотки крови при экспериментальной артериальной гипертензииMetabolic profile of blood serum in experimental arterial hypertensionhttps://orcid.org/0000-0002-8807-2580СеряпинаА. А.SeryapinaA. A.

Новосибирск

Novosibirsk

seryapina@bionet.nsc.ruМалявкоА. А.MalyavkoA. A.

Новосибирск

Novosibirsk

https://orcid.org/0000-0003-2343-5085ПолитыкоЮ. К.PolitykoYu. K.

Новосибирск

Novosibirsk

https://orcid.org/0000-0002-8265-6446ЯньшолеЛ. В.YansholeL. V.

Новосибирск

Novosibirsk

https://orcid.org/0000-0002-1380-3000ЦенталовичЮ. П.TsentalovichYu. P.

Новосибирск

Novosibirsk

https://orcid.org/0000-0002-1550-1647МаркельА. Л.MarkelA. 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 FederationИнститут «Международный томографический центр» Сибирского отделения Российской академии наукРоссияInternational Tomography Center of the Siberian Branch of the Russian Academy of SciencesRussian 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 Federation202308092023275530538Copyright © Серяпина А.А., Малявко А.А., Политыко Ю.К., Яньшоле Л.В., Центалович Ю.П., Маркель А.Л., 20232023Серяпина А.А., Малявко А.А., Политыко Ю.К., Яньшоле Л.В., Центалович Ю.П., Маркель А.Л.Seryapina A.A., Malyavko A.A., Polityko Y.K., Yanshole L.V., Tsentalovich Y.P., Markel A.L.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/3862

Этиология гипертонической болезни неочевидна, поскольку одновременно оказываются задействованы различные системы организма, тем или иным образом связанные с регуляцией артериального давления: симпатическая нервная, ренин-ангиотензин-альдостероновая и гипоталамо-гипофизарно-надпочечниковая системы, почечные и эндотелиальные механизмы. На патогенез гипертонической болезни влияет множество как генетических, так и средовых факторов, что обусловливает популяционную гетерогенность заболевания у людей. В связи с этим возникает необходимость в проведении исследований на экспериментальных моделях – инбредных линиях животных. Таковой является линия крыс НИСАГ (ISIAH), воспроизводящая наследственную индуцированную стрессом артериальную гипертензию, максимально приближенную к артериальной гипертонии у людей. Для определения специфических маркеров заболеваний используются «омиксные» технологии, в том числе метаболомные, которые дают представление о профиле концентраций низкомолекулярных соединений – аминокислот, липидов, углеводов, фрагментов нуклеиновых кислот – в биологических образцах, доступных для клинического анализа (кровь и моча). В настоящей работе проведен анализ метаболомного профиля сыворотки крови самцов крыс линии НИСАГ с генетической стресс-зависимой формой артериальной гипертензии по сравнению с нормотензивной линией крыс WAG. С применением метода спектроскопии ядерно-магнитного резонанса (ЯМР-спектроскопия) в образцах сыворотки крови было идентифицировано 56 метаболитов, при этом для 18 метаболитов выявлены достоверные различия по концентрации в сыворотке крови между линиями крыс. Статистический анализ полученных данных показал, что гипертензивный статус крыс НИСАГ характеризуется сочетанным повышением концентраций лейцина, изолейцина, валина, мио-инозитола, изобутирата, глутамата, глутамина, орнитина и креатинфосфата и понижением концентраций 2-гидроксиизобутирата, бетаина, тирозина и триптофана. Такие изменения концентраций метаболитов ассоциированы с характерными для гипертензивного статуса изменениями в регуляции метаболизма глюкозы (метаболомные маркеры – лейцин, изолейцин, валин и мио-инозитол), синтеза оксида азота (орнитин) и катехоламинов (тирозин) и с воспалительными процессами (метаболомные маркеры – бетаин, триптофан). Таким образом, идентификация метаболомного профиля стресс-зависимой формы артериальной гипертонии представляется важным результатом, полезным для разработки персонализированного подхода к профилактике и лечению гипертонической болезни.

The etiology of essential hypertension is intricate, since it employs simultaneously various body systems related to the regulation of blood pressure in one way or another: the sympathetic nervous system, renin-angiotensin-aldosterone and hypothalamic-pituitary-adrenal systems, renal and endothelial mechanisms. The pathogenesis of hypertension is influenced by a variety of both genetic and environmental factors, which determines the heterogeneity of the disease in human population. Hence, there is a need to perform research on experimental models – inbred animal strains, one of them being ISIAH rat strain, which is designed to simulate inherited stress-induced arterial hypertension as close as possible to primary (or essential) hypertension in humans. To determine specific markers of diseases, various omics technologies are applied, including metabolomics, which makes it possible to evaluate the content of low-molecular compounds – amino acids, lipids, carbohydrates, nucleic acids fragments – in biological samples available for clinical analysis (blood and urine). We analyzed the metabolic profile of the blood serum of male ISIAH rats with a genetic stress-dependent form of arterial hypertension in comparison with the normotensive WAG rats. Using the method of nuclear magnetic resonance spectroscopy (NMR spectroscopy), 56 metabolites in blood serum samples were identified, 18 of which were shown to have significant interstrain differences in serum concentrations. Statistical analysis of the data obtained showed that the hypertensive status of ISIAH rats is characterized by increased concentrations of leucine, isoleucine, valine, myo-inositol, isobutyrate, glutamate, glutamine, ornithine and creatine phosphate, and reduced concentrations of 2-hydroxyisobutyrate, betaine, tyrosine and tryptophan. Such a ratio of the metabolite concentrations is associated with changes in the regulation of glucose metabolism (metabolic markers – leucine, isoleucine, valine, myoinositol), of nitric oxide synthesis (ornithine) and catecholamine pathway (tyrosine), and with inflammatory processes (metabolic markers – betaine, tryptophan), all of these changes being typical for hypertensive status. Thus, metabolic profiling of the stress-dependent form of arterial hypertension seems to be an important result for a personalized approach to the prevention and treatment of hypertensive disease.

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