ПРОФИЛЬ МОЛЕКУЛЯРНЫХ МАРКЕРОВ ФИБРОЗА У КРЫС ПРИ ВОЗДЕЙСТВИИ РАЗЛИЧНЫХ ДОЗ ДОКСОРУБИЦИНА
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Ключевые слова

анрациклиновая кардиомиопатия
доксорубицин
молекулярные маркеры
сердечная недостаточность
фиброз

Аннотация

Работа посвящена исследованию профиля молекулярных маркеров фиброза при введении крысам стока Wistar различных доз доксорубицина. Работа выполнена на 40 самцах крыс стока Wistar весом 260 ± 19 гр. Животные были разделены на 4 группы: контроль и три опытные группы с определенной частотой введения (6 раз через два дня) и определенной дозой доксорубицина (5, 10, 15 мг/кг, внутрибрюшинно). По окончании введения химиопрепарата наблюдение за животными составляло 2 месяца. На момент окончания исследования у наркотизированных животных осуществляли забор сердца для проведения молекулярных и морфологических исследований. Гистологический, эхокардиографический и молекулярный анализы выявили дозозависимые повреждающие изменения миокарда левого желудочка на фоне воздействия различных доз доксорубицина. Уровень экспрессии TGF-β не отличался от контрольных значений через 2 месяца после окончания введения всех кумулятивных доз химиопрепарата. Однако на данном этапе исследования сохраненная повышенная экспрессия коллагена I, II типа, ET-1, FGF4 и TNF-α, была характерна для животных, получавших максимальную кумулятивную дозу доксорубицина, что может отражать незавершенность процесса формирования фиброзной ткани, а также их активное участие в развитии воспалительных процессов при выраженном кардиотоксическом повреждении на фоне воздействия химиопрепарата. Для животных, получавших 10 мг/кг наблюдалось отсутствие изменений данных молекулярных маркеров фиброза по сравнению с контрольной группой, тогда как у группы животных с минимальной кумулятивной дозой препарата выявилось снижение экспрессии COL I, II типа, ET-1, TNF-α и увеличение уровня FGF4.

https://doi.org/10.31857/S0044452923020043
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