gastro-jРоссийский журнал гастроэнтерологии, гепатологии, колопроктологииRussian Journal of Gastroenterology, Hepatology, Coloproctology1382-43762658-6673«Gastro» LLC10.22416/1382-4376-2022-32-4-50-67gastro-j-678Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL ARTICLESЖирные кислоты мембран эритроцитов и сыворотки крови для дифференциальной диагностики воспалительных заболеваний кишечникаFatty Acids of Erythrocyte Membranes and Blood Serum in Differential Diagnosis of Inflammatory Bowel Diseaseshttps://orcid.org/0000-0003-0077-3823КручининаМ. В.KruchininaM. V.

Кручинина Маргарита Витальевна — доктор медицинских наук, доцент; ведущий научный сотрудник, заведующая лабораторией гастроэнтерологии; профессор кафедры пропедевтики внутренних болезней

630091, г. Новосибирск, Красный проспект, д. 52;630089, г. Новосибирск, ул. Б. Богаткова, д. 175/1

Margarita V. Kruchinina – Dr. Sci. (Med.), Associate Professor; Leading Researcher, Head of the Gastroenterology Laboratory; Professor of the Department of Propaedeutics of Internal Diseases 

630091, Novosibirsk, Krasny ave., 52630089, Novosibirsk, B. Bogatkov str., 175/1 

kruchmargo@yandex.ruСветловаИ. О.SvetlovaI. O.

Светлова Ирина Олеговна — кандидат медицинских наук, доцент; доцент кафедры терапии, гематологии и трансфузиологии факультета повышения квалификации и переподготовки врачей; врач-гастроэнтеролог630089, г. Новосибирск, ул. Б. Богаткова, д. 175/1;630091, г. Новосибирск, Красный проспект, д. 52 

Irina O. Svetlova — Cand. Sci. (Med.), Associate Professor; Associate Professor of the Department of Therapy, Hematology and Transfusiology of the Faculty of Advanced Training and Retraining of Doctors; Gastroenterologist 

630089, Novosibirsk, B. Bogatkov str., 175/1.630091, Novosibirsk, Krasny ave., 52 

iosvetlova@yandex.ruhttps://orcid.org/0000-0002-5156-2842ОсипенкоМ. Ф.OsipenkoM. F.

Осипенко Марина Федоровна — доктор медицинских наук, профессор; заведующая кафедрой пропедевтики внутренних болезней

630091, г. Новосибирск, Красный проспект, д. 52

Marina F. Osipenko — Dr. Sci. (Med.), Professor; Head of the Department of Propaedeutics of Internal Diseases

630091, Novosibirsk, Krasny ave., 52 

ngma@bk.ruАбалтусоваН. В.AbaltusovaN. V.

Абалтусова Наталья Владиславовна — врач-гастроэнтеролог 630089, г. Новосибирск, ул. Б. Богаткова, д. 175/1 

Natalia V. Abaltusova — Gastroenterologist

630089, Novosibirsk, B. Bogatkov str., 175/1 

abaltusova79@mail.ruhttps://orcid.org/0000-0001-9254-4192ГромовА. А.GromovA. A.

Громов Андрей Александрович — кандидат медицинских наук; старший научный сотрудник лаборатории клинических биохимических и гормональных исследований терапевтических заболеваний

630089, г. Новосибирск, ул. Б. Богаткова, д. 175/1

Andrey A. Gromov — Cand. Sci. (Med.), Senior Researcher at the Laboratory of Clinical Biochemical and Hormonal Studies of Therapeutic Diseases

630089, Novosibirsk, B. Bogatkov str., 175/1 

gromov.center@rambler.ruhttps://orcid.org/0000-0001-9022-1525ШашковМ. В.ShashkovM. V.

Шашков Михаил Вадимович — кандидат химических наук, научный сотрудник аналитической лаборатории

630090, г. Новосибирск, проспект Академика Лаврентьева, д. 5

Mikhail V. Shashkov — Cand. Sci. (Chem.), Researcher at the Analytical Laboratory

630090, Novosibirsk, Akademician Lavrentiev ave., 5 

shashkov@catalysis.ruhttps://orcid.org/0000-0001-5227-9996СоколоваА. С.SokolovaA. S.

Соколова Анастасия Сергеевна — кандидат химических наук, научный сотрудник лаборатории физиологически активных веществ

630090, г. Новосибирск, проспект Академика Лаврентьева, д. 9

Anastasia S. Sokolova — Cand. Sci. (Chem.), Researcher at the Laboratory of Physiologically Active Substances

630090, Novosibirsk, Akademician Lavrentiev ave., 9 

a.s_sokolova@mail.ruhttps://orcid.org/0000-0002-3265-8865ЯковинаИ. Н.YakovinaI. N.

Яковина Ирина Николаевна — кандидат технических наук; доцент кафедры электропривода и автоматизации промышленных установок

630073, г. Новосибирск, проспект Карла Маркса, д. 20

Irina N. Yakovina — Cand. Sci. (Tech.); Associate Professor of the Department of Computer Engineering of Electric Drive and Automation of Industrial Installations

630073, Novosibirsk, Karl Marx ave., 20 

i1i2i3@bk.ruБорисоваА. В.BorisovaA. V.

Борисова Анжела Вячеславовна — ординатор

630089, г. Новосибирск, ул. Б. Богаткова, д. 175/1 

Angela V. Borisova — Resident

630089, Novosibirsk, B. Bogatkov str., 175/1 

angelanizelnik@yandex.ruНаучно-исследовательский институт терапии и профилактической медицины — филиал ФГБНУ «Федеральный исследовательский центр “Институт цитологии и генетики” Сибирского отделения Российской академии наук»; ФГБОУ ВО «Новосибирский государственный медицинский университет» Министерства здравоохранения Российской ФедерацииРоссияResearch Institute of Internal and Preventive Medicine — Branch of the Institute of Cytology and Genetics, Siberian branch of Russian Academy of Sciences; Novosibirsk State Medical UniversityRussian FederationФГБОУ ВО «Новосибирский государственный медицинский университет» Министерства здравоохранения Российской ФедерацииРоссияNovosibirsk State Medical UniversityRussian FederationНаучно-исследовательский институт терапии и профилактической медицины — филиал ФГБНУ «Федеральный исследовательский центр “Институт цитологии и генетики” Сибирского отделения Российской академии наук»РоссияResearch Institute of Internal and Preventive Medicine — Branch of the Institute of Cytology and Genetics, Siberian branch of Russian Academy of SciencesRussian FederationФГБУН «Федеральный исследовательский центр "Институт катализа им. Г.К. Борескова" Сибирского отделения Российской академии наук»РоссияBoreskov Institute of Catalysis, Siberian branch of Russian Academy of SciencesRussian FederationФГБУН «Новосибирский институт органической химии им. Н.Н. Ворожцова» Сибирского отделения Российской академии наукРоссияNovosibirsk Institute of Organic Chemistry, Siberian branch of Russian Academy of SciencesRussian FederationФГБОУ ВО «Новосибирский государственный технический университет»РоссияNovosibirsk State Technical UniversityRussian Federation2022300920223245067Copyright © Кручинина М.В., Светлова И.О., Осипенко М.Ф., Абалтусова Н.В., Громов А.А., Шашков М.В., Соколова А.С., Яковина И.Н., Борисова А.В., 20222022Кручинина М.В., Светлова И.О., Осипенко М.Ф., Абалтусова Н.В., Громов А.А., Шашков М.В., Соколова А.С., Яковина И.Н., Борисова А.В.Kruchinina M.V., Svetlova I.O., Osipenko M.F., Abaltusova N.V., Gromov A.A., Shashkov M.V., Sokolova A.S., Yakovina I.N., Borisova A.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.gastro-j.ru/jour/article/view/678

Цель исследования: изучить уровни жирных кислот мембран эритроцитов (Эр) и сыворотки крови (СК) у пациентов с воспалительными заболеваниями кишечника для создания дифференциально-диагностических моделей, включающих жирные кислоты в качестве биомаркеров, для различения нозологических форм ВЗК (язвенного колита — ЯК, болезни Крона — БК, неклассифицируемого колита — НКК).Материалы и методы. Обследовано 110 пациентов (средний возраст 37,7 ± 12,1 года) с ВЗК и 53 обследуемых группы сравнения (43,3 ± 11,7 года). Группа пациентов с ВЗК включала в себя больных с ЯК — 50 человек, с БК — 41 человек и 19 пациентов с НКК. У 42 пациентов (84 %) с ЯК, 34 пациентов с БК (82,9 %) и 11 человек с НКК (57,9 %) выявлено обострение заболевания. Исследование состава жирных кислот (ЖК) мембран Эр и СК проведено с помощью ГХ/МС системы на основе трех квадруполей Agilent 7000B (США).Результаты. Наиболее значимыми для различения активного ЯК от обострения БК оказались сывороточные уровни элаидиновой (p = 0,0006), докозатетраеновой (n-6) (p = 0,004), докодиеновой (n-6) (p = 0,009) кислот, отношение омега-3/омега-6 (p = 0,02), докозапентаеновой кислоты (n-3) (p = 0,03); суммы двух омега-3 ПНЖК: эйкозапентаеновой и докозагексаеновой (p = 0,03), а также содержание лауриновой ЖК Эр (p = 0,04) (AUC — 0,89, чувствительность — 0,91, специфичность — 0,89, диагностическая точность — 0,91). Для различения активного ЯК от стадии обострения НКК оказались значимыми следующие ЖК СК: альфа-линоленовая, насыщенные (пентадекановая, пальмитиновая, стеариновая, арахиновая), мононенасыщенные (пальмитолеиновая, олеиновая), омега-6 (гексадекадиеновая, арахидоновая) (p = 0,00000011–0,03300000), (AUC — 0,995, чувствительность — 0,98; специфичность — 0,96; диагностическая точность — 0,97). Наиболее значимыми для различения пациентов с активной БК от обострения НКК оказались уровни ЖК: альфа-линоленовой, пальмитолеиновой, олеиновой, суммы насыщенных жирных кислот (НЖК), суммы ненасыщенных жирных кислот (ННЖК), стеариновой; суммы мононенасыщенных жирных кислот (МНЖК); отношения НЖК/ННЖК; НЖК/ПНЖК (полиненасыщенные жирные кислоты); линолевой; суммы омега-6 ПНЖК; лауриновой; арахиновой (p = 0,0000000017–0,0300000000) (AUC — 0,914, чувствительность — 0,90; специфичность — 0,87, диагностическая точность — 0,91).Заключение. Исследование уровней жирных кислот в группах с разными нозологическими формами ВЗК с помощью комплексного статистического анализа, включая методы машинного обучения, позволило создать диагностические модели, дифференцирующие БК, ЯК и НКК в стадии обострения с высокой точностью. Предложенный подход представляется перспективным для дифференциальной диагностики нозологических форм ВЗК.

Aim: to study fatty acid levels in erythrocyte membranes (RBC) and blood serum (BS) in patients with inflammatory bowel diseases (IBDs) to develop differential diagnostic models including fatty acids as biomarkers to distinguish between nosological entities of IBDs (ulcerative colitis — UC, Crohn's disease — CD, unclassified colitis — UCC).Materials and methods. We examined 110 patients (mean age 37,7 ± 12,1 years) with IBDs and 53 healthy patients in control group (43,3 ± 11,7 years). The IBDs group included 50 patients with UC, 41 patients with CD, 19 patients with UCC. An exacerbation of the disease was revealed in 42 patients (84 %) with UC, 34 patients with CD (82.9 %) and 11 people with UCC (57.9 %). The study of fatty acids (FA) composition of RBC membranes and BS was carried out using GC/MS system based on three Agilent 7000B quadrupoles (USA).Results. The most significant for distinguishing active UC from CD exacerbation were serum levels of elaidin (p = 0.0006); docosatetraenoic (n-6) (p = 0.004); docodienic (n-6) (p = 0.009); omega-3/omega-6 ratio (p = 0.02); docosapentaenoic (n-3) (p = 0.03); the sum of eicosapentaenoic and docosahexaenoic (p = 0.03), as well as the content of RBC lauric FA (p = 0.04) (AUC — 0.89, sensitivity — 0.91, specificity — 0.89, diagnostic accuracy — 0.91). To distinguish active UC from the same of UCC, the following serum FA were found to be significant: alpha-linolenic; saturated (pentadecanoic, palmitic, stearic, arachidic); monounsaturated (palmitoleic, oleic); omega-6 (hexadecadienic, arachidonic) (p = 0.00000011—0.03300000) (AUC — 0.995, sensitivity — 0.98, specificity — 0.96, diagnostic accuracy — 0.97). The most significant in distinguishing patients with active CD from UCC exacerbation were levels of the following FA: alpha-linolenic; palmitoleic; oleic; the amount of saturated fatty acids (SFA); total unsaturated fatty acids (UFA); stearic; monounsaturated fatty acids (MUFA) amount; SFA/UFA; SFA/PUFA (polyunsaturated fatty acids); linoleic; total PUFA n6; lauric; arachidic acid (p = 0.0000000017–0.030000000) (AUC — 0.914, sensitivity — 0.90, specificity — 0.87, diagnostic accuracy — 0.91).Conclusion. The study of FA levels in groups with different nosological forms of IBDs using complex statistical analysis, including machine learning methods, made it possible to create diagnostic models that differentiate CD, UC and UCC in the acute stage with high accuracy. The proposed approach is promising for the purposes of differential diagnosis of nosological forms of IBDs.

воспалительные заболевания кишечниканозологические формыдифференциальная диагностикажирные кислотыэритроцитысыворотка кровиinflammatory bowel diseasesnosological formsdifferential diagnosisfatty acidserythrocytesblood serumРабота выполнена в рамках темы «Эпидемиологический мониторинг состояния здоровья населения и изучение молекулярно-генетических и молекулярно-биологических механизмов развития распространенных терапевтических заболеваний в Сибири для совершенствования подходов к их диагностике, профилактике и лечению» ГЗ № 0324-2018-0001, Рег. № АААА-А17-117112850280-2.This research has been carried out within the framework of the topic “Epidemiological monitoring of public health and study of molecular-genetic and molecular-biological mechanisms of development of common therapeutic diseases in Siberia to improve approaches to their diagnosis, prevention and treatment” GZ No. 0324-2018-0001, Reg. 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The authors declare that there are no conflicts of interest present.