mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-ROL-2863mimmun-2863Research ArticleОБЗОРЫREVIEWSРоль липополисахарида в формировании микроваскулярных осложнений при сахарном диабете 1-го типаRole of lipopolysaccharide in genesis of microvascular complications in type 1 diabetes mellitusБелоглазовВ. А.BeloglazovV. A.

Белоглазов В.А. – д.м.н., профессор, заведующий кафедрой внутренней медицины № 2 

г. Симферополь, Республика Крым

Beloglazov V.A., PhD, MD (Medicine), Professor, Head, Department of Internal Medicine No. 2 

Simferopol, Republic of Crimea

ЯцковИ. А.YatskovI. A.

Яцков И.А. – ассистент кафедры внутренней медицины № 2 

г. Симферополь, Республика Крым

 

Yatskov I.A., Assistant Professor, Department of Internal Medicine No. 2 

Simferopol, Republic of Crimea

egermd@yandex.ruУльяноваД. И.UlyanovaD. I.

Ульянова Д.И. – студентка кафедры внутренней медицины № 2 

г. Симферополь, Республика Крым

Ulyanova D.I., Student, Department of Internal Medicine No. 2 

Simferopol, Republic of Crimea

Медицинская академия имени С.И. Георгиевского ФГАОУ ВО «Крымский федеральный университет имени В.И. Вернадского»РоссияS. Georgievsky Medical Academy, V. Vernadsky Crimean Federal UniversityRussian Federation20241610202326611391148Copyright © Белоглазов В.А., Яцков И.А., Ульянова Д.И., 20242024Белоглазов В.А., Яцков И.А., Ульянова Д.И.Beloglazov V.A., Yatskov I.A., Ulyanova D.I.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.mimmun.ru/mimmun/article/view/2863

Несмотря на существенные успехи, достигнутые в разработке патогенетических методов лечения пациентов с сахарным диабетом 1-го типа (СД1), и снижение смертности у данной категории больных, по сравнению с общей популяцией разница в ожидаемой продолжительности жизни у пациентов СД1 в возрасте 20 лет составляет около 10-12 лет. Одной из наиболее важных проблем в ведении пациентов с СД1 на данный момент является наличие микрососудистых осложнений, повышающих риск развития сердечно-сосудистых заболеваний (ССЗ) и общей смертности. Избыточный риск сохраняется даже при надлежащем контроле всех факторов риска ССЗ, что определяет необходимость углубленных исследований для уточнения и выявления всех факторов развития и прогрессирования микрососудистых осложнений у пациентов с СД1, а также разработки методов их модификации и коррекции. По данным литературы, основными патогенетическими звеньями развития микрососудистых осложнений при СД1 являются процессы прямого повреждения эндотелия, опосредованного глюкозой, окислительный стресс, а также фибротические процессы микрососудистого русла, в данном литературном обзоре основное внимание сконцентрировано на описании дополнительного возможного пути развития данных изменений – хроническом воздействии повышенной концентрации липополисахарида граммнегативной флоры (LPS) в системном кровотоке. LPS, повышая генерацию реактивных форм кислорода, через НАДФ-оксидазу приводит к существенному снижению биодоступности эндотелиального NO и развитию эндотелиальной дисфункции (ЭД). Активация толл-подобных рецепторов 4-го типа (TLR4) сопровождается включением p38MAPK и последующей транслокацией NF-κB в ядро, увеличивая транскрипцию гена интерлейкина-6 (IL-6) и молекул адгезии (ICAM-1, VCAM-1 и E-селектина). LPS способен ингибировать противовоспалительное действие TGF-β, повышая количество поляризованных М1-макрофагов и приводя к персистенции воспаления, активировать рецепторы TGFBR1, усиливая экспрессию гена PAI-1, повышая риск атерогенеза и тромбообразования в сосудистом русле. Представленные в данном литературном обзоре данные свидетельствуют о наличии возможной оси «LPS-кишечник-микрососудистая сеть», являющейся важным патогенетическим компонентом микроваскулярных осложнений у пациентов с СД1. Хроническое избыточное поступление LPS в системный кровоток может приводить к развитию персистирующего низкоинтенсивного воспаления, сопровождающегося изменением архитектоники экстрацеллюлярного матрикса, потенцировать развитие эндотелиальной дисфункции и сосудистого воспаления. Направление изучения влияния LPS на течение СД1 является перспективным направлением и требует дальнейших более глубоких научных изысканий.

Despite significant advances in pathogenetic treatments for patients with diabetes mellitus type 1 (DM1) and reduction of mortality in this cohort of patients, as compared with general population, the difference in life expectancy in DM1 patients at the age of 20 years is about 10-12 years. Microvascular complications that increase the risk of cardiovascular disease (CVD) and overall mortality represent one of the most important problems in management of patients with DM1. The excessive risks persist even with proper control of all CVD risk factors, thus determining the need for in-depth research, in order to clarify and identify all factors of development and progression of microvascular complications in patients with DM1, as well as to develop methods for their modification and correction. According to current literature, the main pathogenetic links in the development of microvascular complications in DM1 concern, e.g., direct glucosemediated endothelial damage, oxidative stress, as well as microvascular fibrotic processes. In this review article, we consider additional possible route of these changes, i.e., chronic exposure to increased burden of bacterial lipopolysaccharide (LPS) derived from Gram-negative flora retained in systemic blood flow. LPS, by promoting generation of reactive oxygen species via NADPH-oxidase, thus leading to a significantly decreased bioavailability of endothelial NO and development of endothelial dysfunction (ED). Activation of toll-like receptor type 4 (TLR4) is accompanied by activation of p38MAPK, and subsequent translocation of NF-κB to the nucleus, increasing transcription of the interleukin-6 (IL-6) gene and adhesion molecules (ICAM-1, VCAM-1 and E-selectin). LPS is able to inhibit the anti-inflammatory effect of TGF-β, increasing the number of polarized M1 macrophages and leading to persistence of inflammation, activate TGFBR1 receptors, promotes PAI-1 gene expression, thus increasing the risk of atherogenesis and thrombosis in the vascular bed. The data presented in this literature review suggest a possible “LPS-gut-microvascular network” axis, which is an important pathogenic component of microvascular complications in patients with DM1. Chronic excessive intake of LPS into the systemic bloodstream can lead to the development of persistent low-grade inflammation accompanied by changes in architectonics of extracellular matrix, potentiate the development of endothelial dysfunction and vascular inflammation. The studies of LPS effects upon clinical course of DM1 are promising and require further in-depth research.

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