mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-2018-6-833-846mimmun-1668Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESИММУНОРЕГУЛЯТОРНЫЙ ДИСБАЛАНС И СТРУКТУРНО- ФУНКЦИОНАЛЬНОЕ СОСТОЯНИЕ СЕРДЦА У ПАЦИЕНТОВ С САХАРНЫМ ДИАБЕТОМ 2 ТИПАIMMUNOREGULATORY IMBALANCE AND FUNCTIONAL STATE OF THE HEART IN THE PATIENTS WITH DIABETES MELLITUS TYPE 2КологривоваИ. В.KologrivovaI. V.

к.м.н., научный сотрудник отделения функциональной и лабораторной диагностики, Научно-исследовательский институт кардиологии

634012, Россия, г. Томск, ул. Киевская, 111а.Тел.: 8 (913) 105-38-69

PhD (Medicine), Research Associate, Department of Functional and Laboratory Diagnostics

634012, Russian Federation, Tomsk, Kievskaya str., 111a.Phone: 7 (913) 105-38-69

ikologrivova@gmail.comСусловаТ. Е.SuslovaT. E.

к.м.н., ведущий научный сотрудник отделения функциональной и лабораторной диагностики

PhD (Medicine), Leading Research Associate, Department of Functional and Laboratory Diagnostics

ВинницкаяИ. В.VinnitskayaI. V.

научный сотрудник отделения атеросклероза и хронической ишемической болезни сердца

Research Associate, Department of Atherosclerosis and Chronic Ischemic Heart Disease

КошельскаяО. А.KoshelskayaO. A.

д.м.н., профессор, ведущий научный сотрудник отделения атеросклероза и хронической ишемической болезни сердца

PhD, MD (Medicine), Professor, Leading Research Associate, Department of Atherosclerosis and Chronic Ischemic Heart Disease

БощенкоА. А.BoshchenkoA. A.

д.м.н., старший научный сотрудник отделения атеросклероза и хронической ишемической болезни сердца, заместитель директора по научной работе

ТрубачеваО. А.TrubachevaO. A.

к.м.н., научный сотрудник отделения функциональной и лабораторной диагностики

PhD (Medicine), Research Associate, Department of Functional and Laboratory Diagnostics

ФГБНУ «Томский национальный исследовательский медицинский центр Российской академии наук», г. Томск ФГБОУ ВО «Сибирский государственный медицинский университет» Министерства здравоохранения РФ, г. ТомскРоссияTomsk National Research Medical Centre Siberian State Medical UniversityRussian FederationФГБНУ «Томский национальный исследовательский медицинский центр Российской академии наук», г. ТомскРоссияTomsk National Research Medical CentreRussian Federation201813122018206833846Copyright © Кологривова И.В., Суслова Т.Е., Винницкая И.В., Кошельская О.А., Бощенко А.А., Трубачева О.А., 20182018Кологривова И.В., Суслова Т.Е., Винницкая И.В., Кошельская О.А., Бощенко А.А., Трубачева О.А.Kologrivova I.V., Suslova T.E., Vinnitskaya I.V., Koshelskaya O.A., Boshchenko A.A., Trubacheva O.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.mimmun.ru/mimmun/article/view/1668

Сахарный диабет 2-го типа относится к наиболее социально значимым неинфекционным заболеваниям современности и является важным фактором риска развития сердечно-сосудистых заболеваний. Изменения в диастолической функции миокарда левого желудочка отмечаются у пациентов с диабетом независимо от наличия других осложнений. Этиология сердечной недостаточности при сахарном диабете 2-го типа носит многофакторный характер и связана с клеточными, молекулярными и метаболическими причинами, однако патофизиологический механизм ее развития до конца не изучен. Целью настоящей работы стала оценка содержания провоспалительных субпопуляций Т-лимфоцитов (Т-хелперов 1-го типа [Th1] и Т-хелперов 17-го типа [Th17]) и FoxP3+Т-регуляторных лимфоцитов в зависимости от структурно-функционального состояния сердца по данным двухмерного эхокардиографического исследования у пациентов с сочетанием артериальной гипертензии и сахарного диабета 2-го типа. В ходе одномоментного сравнительного исследования было обследовано 25 пациентов с сочетанием артериальной гипертензии и сахарного диабета 2-го типа и 14 пациентов с артериальной гипертензией без нарушений обмена веществ. Всем пациентам проводили эхокардиографию из трансторакального доступа в М-режиме, B-режиме и доплеровскихрежимах сканирования. Методом проточной цитометрии в периферической крови оценивали содержание Th1- и Th17- лимфоцитов по внутриклеточной продукции CD4+ лимфоцитами IL-17 и IFNγ, соответственно, и FoxP3+Т-регуляторных лимфоцитов по экспрессии CD25 и фактора транскрипции FoxP3. В сыворотке крови методом проточной цитометрии оценивали содержание IL-17, IL-10, IFNγ и TNFα. Установлено наличие корреляционных взаимосвязей между содержанием Th17-лимфоцитов, FoxP3+Т- регуляторных лимфоцитов и структурно-функциональными параметрами миокарда у пациентов с сахарным диабетом 2-го типа, в то время как у пациентов без нарушений углеводного обмена взаимосвязи между иммунологическими и эхокардиографическими параметрами отсутствовали. У пациентов с сахарным диабетом и диастолической дисфункцией содержание FoxP3+Т-регуляторных лимфоцитов, соотношение между Т-регуляторными и Th17-лимфоцитами и средняя интенсивность флуоресценции IL-17 в Th17 были ниже, чем у пациентов с диабетом, но без диастолической дисфункции. Ассоциация диастолической дисфункции с  сахарным диабетом 2-го типа сопровождалась повышением содержания IFNγ+Th1-лимфоцитов и концентрации IL-10, IFNγ и TNFα в сыворотке по сравнению с теми пациентами, у которых диастолическая дисфункция наблюдалась в отсутствие нарушений углеводного обмена. Для диабетических пациентов с диастолической дисфункцией было характерно наличие гиперинсулинемии, гипергликемии, более высокого индекса инсулинорезистентности, увеличение окружности талии и индекса висцерального ожирения по сравнению с пациентами с диастолической дисфункцией без диабета. Висцеральное ожирение и снижение чувствительности тканей к инсулину можно рассматривать в качестве патогенетически значимых факторов развития иммунорегуляторного дисбаланса и диастолической дисфункции у пациентов с сахарным диабетом 2-го типа.

Diabetes mellitus type 2 is one of the most important non-infectious diseases in the modern world, being an important risk factor of cardiovascular disorders. Changes in left ventricular myocardial diastolic function are observed in diabetic patients independently from other comorbidities. Etiology of the heart failure during diabetes mellitus type 2 is multifactorial, exhibiting cellular,  molecular and metabolic aspects. However, its pathophysiological mechanisms are not completely understood. The aim of this study was to evaluate numbers of inflammatory T lymphocytes, i.e., T helper type 1 (Th1) and T helper type 17 (Th17) cells, and FoxP3+T regulatory lymphocytes, depending on the functional state of the heart assessed by two-dimensional echocardiography in patients with arterial hypertension and diabetes mellitus type 2. A total of twenty-five patients with a combination of arterial hypertension and diabetes mellitus type 2, and 14 patients with arterial hypertension without carbohydrate disturbances were recruited to a cross-ectional case-control study. All the patients underwent echocardiography with transthoracic access at the M-mode, B-mode and Doppler mode of imaging. We evaluated numbers of Th1 and Th17 lymphocytes by intracellular production of IL-17 and IFNγ by CD4+ lymphocytes, respectively. The numbers of FoxP3+T regulatory lymphocytes were estimated by expression of CD25 and FoxP3 transcription factor. A flow cytometry approach was used in both cases. We revealed some correlations between the numbers of Th17 lymphocytes, FoxP3+T regulatory lymphocytes and functional parameters of myocardium in patients with diabetes mellitus type 2, which were absent in patientswithout carbohydrate impairments. The numbers of FoxP3+T egulatory lymphocytes, Treg/Th17 lymphocyte ratio, and mean fluorescence intensity of IL-17 for Th17 cells was lower in patients with diabetes mellitus and diastolic dysfunction compared to the patients with diabetes free of diastolic dysfunction. Association of diastolic dysfunction with diabetes mellitus type 2 was accompanied by increase of IFNγ+Th1 lymphocyte numbers and concentrations of IL-10, IFNγ and TNFα in serum as compared to the patients with diastolic dysfunction in the absence of carbohydrate metabolism disturbances. The diabetic patients with diastolic dysfunction were characterized by hyperinsulinemia, hyperglycemia, higher index of insulin resistance, increase of waist circumference and visceral adiposity index when compared to the patients with diastolic dysfunction without diabetes. Visceral obesity and decrease of insulin sensitivity may be regarded as pathogenetically significant factors for the development of immune regulatory imbalance and diastolic dysfunction in the patients with diabetes mellitus type 2.

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