Механизмы защитного действия мезенхимальных мультипотентных стромальных клеток при экспериментальном остром пиелонефрите

Выводы.

1. При введении инокулята из смешанной культуры фекальных бактерий в мочевой пузырь у крыс развивается острый пиелонефрит, который характеризуется диффузной и очаговой, преимущественно нейтрофильной, воспалительной инфильтрацией, развитием окислительного стресса и повышением содержания провоспалительного цитокина ТЫРа в тканях почки. После введения ММСК костного мозга указанные показатели воспалительного процесса снижаются.

2. При экспериментальном остром пиелонефрите трансплантированные ММСК накапливаются в почке более интенсивно, чем в почке животных контрольной группы. Усилению миграции ММСК способствует высокий уровень ТМРа.

3. В условиях сокультивирования с лейкоцитами, активированными липополисахаридом, в ММСК происходит запуск сигнальных путей, обеспечивающих иммуносупрессорные свойства этих клеток, признаками которых является повышение количества трансформирующего ростового фактора (Т6Р1) и индуцибельной 1Ю-синтазы (?N08), а также усиление активности матриксной металлопротеиназы (ММП-2).

4. Сокультивирование с лейкоцитами и липополисахаридом индуцирует в ММСК сигнальные пути, аналогичные путям, активируемым при фармакологическом прекондиционировании 1Ю1, о чем свидетельствует повышение количества фосфорилированной формы киназы гликогенсинтазы (ввК-Зр), ключевого фермента, определяющего устойчивость клеток к окислительному стрессу.

5. Трансплантация ММСК костного мозга после сокультивирования с активированными лейкоцитами снижает признаки воспаления при экспериментальном остром пиелонефрите, что выражается в уменьшении числа лейкоцитов в крови, уровня TNFa и активности миелопероксидазы (МПО) в тканях почки.

6. Инкубация с ЫС1 не приводит к увеличению в ММСК количества Т6(31, ?N03 и активности ММП-2, однако повышает количество фосфорилированной формы СвК-Зр. Влияние таких ММСК на число лейкоцитов в крови и активность МПО в тканях почки при остром пиелонефрите не отличается от действия на эти показатели интакных ММСК. ММСК, сокультивированные с активированными лейкоцитами, вызывают более выраженное уменьшение числа лейкоцитов в крови по сравнению с эффектом нативных ММСК и ММСК, обработанных ЫС1.

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