DOI: https://doi.org/10.30978/MG-2020-4-80

Ендотоксин та метаболічно асоційована патологія

G. D. Fadieienko, O. Y. Gridnyev, S. V. Gridnieva

Анотація


Висвітлено сучасні уявлення щодо ролі мікробіому кишечника в патогенетичних механізмах розвитку метаболічно асоційованих захворювань. Описано історію відкриття ендотоксину. Встановлено багатогранність властивостей ендотоксину щодо як інфекційної, так і неінфекційної патології. Представлено стресову теорію регуляції надходження кишкового ліпополісахариду в загальний кровотік і дані досліджень, які підтверджують її. Наведено також дані щодо фізіологічної ролі ліпополісахариду та його особ­ливості залежно від віку, стресу і фізичного навантаження. Показано основні механізми розвитку ендотоксемії, зокрема роль порушення еубіозу кишкового мікробіому і підвищення кишкової проникності. Висвітлено значення печінки в первинній інактивації ендотоксину у здорових осіб. Показано роль ліпідів у транспортуванні кишкового ліпополісахариду. Описано поняття «ендотоксинова агресія» і «метаболічна ендотоксинова агресія». Установлено значення високожирової дієти в розвитку ендотоксемії, зокрема за рахунок розвитку дисбіозу. Наведено результати експериментальних робіт із введенням ліпополісахариду лабораторним тваринам. Показано, що введення ендотоксину індукує підвищення рівня прозапальних цитокінів. Описано механізми взаємодії ліпополісахариду з Toll‑подібними рецепторами і наслідки цієї взаємодії, зокрема потенціювання хронічного запалення в тканині печінки. Розкрито роль ендотоксинової агресії в процесах індукції запалення низької градації у пацієнтів з ожирінням і взаємозв’язок зі змінами кишкового мікробіому. Показано значення ліпополісахариду в розвитку інсулінорезистентності та цукрового діабету 2 типу. Наведено дані досліджень ролі ендотоксинемії в розвитку неалкогольної жирової хвороби печінки. Встановлено механізм взаємодії ліпополісахариду з клітинами печінки та його значення в прогресуванні неалкогольної жирової хвороби печінки з розвитком стеатогепатиту і фіброзу.


Ключові слова


ліпополісахарид; ендотоксин; ендотоксинова агресія; неалкогольна жирова хвороба печінки; ожиріння

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