Внеклеточная ДНК в медицине неотложных состояний

РЕЗЮМЕ. Для медицины неотложных состояний является актуальным поиск молекул с высокой прогностической ценностью для определения течения и исходов жизнеугрожающих состояний — сепсиса, тяжелых травм, сосудистых катастроф. Одним из перспективных биомаркеров-кандидатов (с англ.: candidate biomarkers — кандидатные биомаркеры) с высоким потенциалом применения в медицине неотложных и критических состояний является содержание внеклеточной ДНК (вкДНК) в плазме крови. Цель данного обзора — выявить перспективы внедрения вкДНК в клиническую медицину и трудности, возникающие на этом пути. Уровень и изменения в динамике концентрации фрагментов циркулирующей ДНК, в том числе органоспецифической фракции вкДНК, на сегодняшний день могут иметь значение для оценки степени повреждения интересующего органа, вероятности осложненного течения и прогноза исходов неотложного/критическо- го состояния у пациентов отделений реанимации и интенсивной терапии. Источниками вкДНК, циркулирующих в кровотоке, могут быть ядра погибающих клеток органов и тканей, поврежденные митохондрии, пул которых обновляется в результате митофагии, а также микроорганизмы. Как патоген-ассоциированные молекулы (PAMP), представленные фрагментами бактериальной и вирусной ДНК, молекулы собственной ДНК, ассоциированные с повреждением (DAMP), связываются с толл-подобными рецепторами (TLR9) и внутриклеточными ДНК-сенсорами (cGAS-STING, NLRP3), инициируя запуск воспалительных процессов в тканях и нарушения гемостаза. Эти процессы носят характер и адаптивных реакций, защищающих от микроорганизмов, и дезадаптивных реакций, потенцирующих повреждения клеток органов. Происходящее усиление экспрессии генов провоспалительных сигнальных путей, ассоциированных с транскрипционным NF-kB и интерферон-регулирующими факторами, в свою очередь способствует продукции цитокинов и других факторов, которые усиливают стресс-реакции, нарушающие функциональную активность клеток в разных органах. Имеющиеся литературные данные свидетельствуют о том, что определение количественного содержания в плазме вкДНК, играющей существенную роль в патогенезе критических/неотложных состояний в качестве PAMP и DAMP, может помочь при обосновании прогноза и своевременной персонализации лечения пациентов с жизнеугрожающими состояниями и недавно их перенесших.

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