Сигнальные механизмы кардиопротекторного эффекта пептидных и непептидных агонистов опиоидных рецепторов при реперфузии сердца (обзор литературы)

Внутригоспитальная смертность у больных острым инфарктом миокарда (ОИМ) составляет 5–8% и в последние годы не снижается. Одной из причин высокой летальности является реперфузионное повреждение сердца. Совершенно очевидно, что существует острая необходимость в разработке препаратов, способных эффективно снизить смертность при ОИМ. Такими препаратами могут стать опиоиды. Активация периферических µ2-, δ2-, κ1-опиоидных рецепторов (ОР) уменьшает размер инфаркта и улучшает сократимость при реперфузии. Периферические µ1-, δ1-, κ2-ОР не участвуют в регуляции толерантности сердца к реперфузионным повреждениям. В кардиопротекторном эффекте опиоидного посткондиционирования принимают участие PI3-киназа (phosphoinositide 3-kinase, PI3K), ERK1/2 (extracellular signal-regulated kinase-1/2), Akt-киназа, рецептор эпидермального фактора роста (epidermal growth factor receptor, EGFR) и растворимая гуанилилциклаза (soluble guanylyl cyclase, sGC). Ингибирование GSK-3β (glycogen synthase kinase-3β) и JNK (c-jun NH2 amino-terminal kinase) вовлечено в опиоидное посткондиционирование, в отличие от Янус-киназы-2 (JAK2) и протеинкиназы A (PKA). Есть доказательства того, что гемоксигеназа-1 (HO-1) и NO-синтаза (NOS) также участвуют в опиоид-индуцированном посткондиционировании. Пептидные и непептидные агонисты µ2-, δ2-, κ1-ОР могут стать препаратами для лечения ОИМ.

Цель обзора: анализ сигнальных механизмов кардиопротекторного эффекта пептидных и непептидных агонистов ОР при реперфузии сердца. Поиск литературы по данному вопросу осуществлялся в базе данных PubMed с использованием запросов по следующим ключевым словам: opioid receptors, opioid receptor agonists, cardioprotective effect of opioid receptor agonists.

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