vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/VJ15.067vavilov-442Research ArticleМОДЕЛИРОВАНИЕ ПАТОЛОГИЙMODELING OF DISORDERS AND EXPERIMENTAL TREATMENTВозможности высокотехнологичного фенотипирования методом спектроскопии ЯМР на примере метаболического отклика печени крыс на воздействие алкоголя и РейшиNMR metabolic profiling of the liver following administrationof alcohol andthemushroom Ganoderma lucidum in ratsКрестинаМ. С.KrestinaM. S.ШевелевО. Б.ShevelevO. B.КоптюгИ. В.KoptyugI. V.ГерлинскаяЛ. А.GerlinskayaL. A.ПельтекС. Е.PeltekS. E.АкуловА. Е.AkulovA. E.akulov_ae@ngs.ruУчреждение Российской академии наук Институт «Международный томографический центр» СО РАН, Новосибирск, Россия Федеральное государственное автономное образовательное учреждение высшего образования «Новосибирский национальный исследовательский государственный университет», Новосибирск, РоссияРоссияInternational Tomography Center of the Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia Novosibirsk State University, Novosibirsk, RussiaRussian FederationФедеральное государственное бюджетное научное учреждение «Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук», Новосибирск, РоссияРоссияInstitute of Cytology and Genetics SB RAS, Novosibirsk, RussiaRussian FederationУчреждение Российской академии наук Институт «Международный томографический центр» СО РАН, Новосибирск, РоссияРоссияInternational Tomography Center of the Siberian Branch of the Russian Academy of Sciences, Novosibirsk, RussiaRussian Federation201501122015194499504Copyright © Крестина М.С., Шевелев О.Б., Коптюг И.В., Герлинская Л.А., Пельтек С.Е., Акулов А.Е., 20152015Крестина М.С., Шевелев О.Б., Коптюг И.В., Герлинская Л.А., Пельтек С.Е., Акулов А.Е.Krestina M.S., Shevelev O.B., Koptyug I.V., Gerlinskaya L.A., Peltek S.E., Akulov A.E.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/442

Для оценки эффективности спектроскопии протонного ядерно-магнитного резонанса (1H ЯМР) как метода метаболомного фенотипирования и метода детектирования ранних метаболических изменений при токсических воздействиях было проведено метаболическое профилирование печени крыс. Образцы тканей были взяты у трех групп крыс: группа К – контрольные животные; группа А – животные, получавшие многократно 15-процентный раствор алкоголя, прием которого не вызывал патологических изменений печени, но стимулировал пролиферацию гепатоцитов, и алкоголя в сочетании с растительным гепатопротекторным препаратом Рейши, Ganoderma lucidum, (группа А +Р). Как следует из полученных результатов, изменения концентрации метаболитов в печени, наблюдаемые в группе А, отражали типичную метабо- лическую реакцию на прием алкоголя и выражались в снижении содержания глицина, лейцина, изолейцина, валина, холина и лактата, а также в повышении уровня ТМАО. При приеме Рейши у крыс группы А +Р восстанавливалась концентрация глицина, валина и ТМАО. Кроме того, в группе А +Р было отмечено увеличение относительно контроля концентрации НАД, АТФ, УТФ, сукцината, пиранозы и ацетата. Индивидуальные вариации содержания валина, изолейцина, лейцина, лактата, холина и пиранозы коррелировали с числом двуядерных гепатоцитов как индикатором пролиферативной активности. Таким образом, исследование тканей печени методом спектроскопии ЯМР 1Н позволяет выявить ранние отклонения уровня метаболитов при хроническом потреблении небольших доз алкоголя и может быть перспективным подходом как для диагностического выявления алкогольного повреждения печени, так и для оценки эффективности применяемой лекарственной терапии.

We have evaluated the efficiency of a metabonomic approach to metabolic phenotyping and detection of early metabolic changes under a toxic influence. For this purpose, a metabolic profiling of rat liver was performed with 1H NMR spectroscopy. Rat tissues from animals in three groups were analyzed. Group C consisted of control animals; animals in group A received alcohol repeatedly (15 % ethanol); and animals in group A+ R received alcohol in combination with a hepatoprotective herbal medicine (Reishi, Ganoderma lucidum) repeatedly. Noteworthy, alcohol consumption did not cause pathological changes, but stimulated hepatocyte proliferation. Our data suggest that changes in metabolite concentrations in A represent a typical metabolic response to alcohol consumption, namely decrease in glycine, leucine, isoleucine, valine, choline and lactate content, and increase in TMAO content. Treatment with Reishi (A+ R) had positive effects, in that it restored the levels of glycine, valine and TMAO. Furthermore, increase in NAD, ATP, UTP, succinate, pyranose, and acetate concentrations was observed in A+ R. A correlation was found between the valine, isoleucine, lactate, cho­line, and pyranose content and the num­ber of binuclear hepatocytes. Binuclear hepatocytes indicate proliferative activity, and the concentration of the metabolites participating in the formation of new hepatic cells decreases. Thus, the study of liver tissues by 1H NMR spectroscopy allows for detection of early changes in metabolite concentra­tions following chronic consumption of alcohol at insignificant doses. Consequently, 1H NMR spectro­scopy can serve as a promising approach to detecting alcohol-related liver pathologies and assessing the efficiency of the therapy used.

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