Молекулярные механизмы регуляции боли у больных остеоартрозом

Цель – изучение механизмов, определяющих уровень боли, на основании анализа профилей экспрессии генов, участвующих в деструкции суставного хряща, воспалении и регуляции метаболизма в крови больных остеоартрозом (ОА) с разными уровнями экспрессии гена mTOR (Mammalian Target Of Rapamycin) и на разных стадиях заболевания.

Материал и методы. Работа проведена на образцах периферической крови 47 амбулаторных больных ОА; 21 больного с поздней стадией ОА, госпитализированного для эндопротезиования коленного сустава, и 27 здоровых людей, составивших контрольную группу (средний возраст – 60,0±7,1; 56,6±8,9 и 58,6±8,3 года соответственно), а также образцов суставного хряща, полученных при оперативном лечении у 21 больного ОА и при аутопсии у 14 здоровых ранее лиц (средний возраст – 38,2±4,3 года), погибших в результате травмы. Состояние больных оценивали по данным клинического, рентгенологического, ультразвукового и денсито- метрического исследования. Общую РНК выделяли из крови и после обратной транскрипции использовали для определения уровня экспрессии генов в полимеразной цепной реакции в режиме реального времени.

Результаты и обсуждение. В подгруппе с низкой экспрессией гена mTOR экспрессия всех исследованных генов оказалась на уровне контроля, за исключением гена матриксной металлопротеиназы 9 (ММП9), экспрессия которого была значительно выше. У больных с высокой экспрессией гена mTOR и больных на поздней стадии ОА экспрессия всех исследованных генов была значительно выше, чем в контроле. Обнаружена положительная корреляция экспрессии генов трансформирующего ростового фактора β1 (TРФβ1; r=0,594; p=0,005) и катепсина К (r=0,595; p=0,003) в крови и суставном хряще больных ОА на поздней стадии заболевания.

Заключение. Разные уровни боли у больных ОА с разными уровнями экспрессии гена mTOR могут быть связаны с соотношением экспрессии генов ММП9 и тканевого ингибитора металлопротеиназ 1 (ТИМП1), избыточной или недостаточной активностью гена mTOR, а также с экспрессией факторов роста – TРФβ1 и сосудистого эндотелиального фактора роста, участвующих в процессах регенерации тканей. 

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