Hong Jinback, Sigg Daniel C, Coles James A, Oeltgen Peter R, Harlow Henry J, Soule Charles L, Iaizzo Paul A
Department of Biomedical Engineering, University of Minnesota, Minneapolis, Minnesota, USA.
Muscle Nerve. 2005 Aug;32(2):200-7. doi: 10.1002/mus.20354.
A link between the cardioprotective benefits of pharmacological preconditioning and natural mammalian hibernation is considered to involve the cellular activation of opioid receptors and subsequent opening of K(ATP) channels. In previous studies, we have demonstrated the protective effects of specific delta-opioid agonists against porcine cardiac ischemia/reperfusion injury. We hypothesize here that preincubation with hibernation induction trigger (HIT) should confer a similar protection in skeletal muscles. Therefore, muscle bundles from swine were pretreated with plasma from hibernating woodchucks (HWP) for 30 min, then exposed to hypoxia for 90 min and reoxygenation for 120 min. Stimulated twitch forces were assessed. The functional effects of pretreatment with nonhibernation (summer) woodchuck plasma, a K(ATP) blocker, or opioid antagonist were also studied. During the reoxygenation period, significantly greater force recoveries were observed only for bundles pretreated with HWP; this response was blocked by naloxone (P < 0.05). We conclude that HIT pretreatment could be used to confer protection against hypoxia/reperfusion injury of skeletal muscles of nonhibernators; it could potentially be utilized to prevent injury during surgical procedures requiring ischemia.
药理学预处理的心脏保护作用与哺乳动物自然冬眠之间的联系被认为涉及阿片受体的细胞激活以及随后ATP敏感性钾通道（K(ATP)通道）的开放。在先前的研究中，我们已经证明了特定的δ-阿片受体激动剂对猪心脏缺血/再灌注损伤具有保护作用。我们在此假设，用冬眠诱导触发因子（HIT）进行预孵育应该能在骨骼肌中赋予类似的保护作用。因此，将来自猪的肌束用冬眠土拨鼠的血浆（HWP）预处理30分钟，然后暴露于缺氧环境90分钟，再复氧120分钟。评估刺激后的抽搐力。还研究了用非冬眠（夏季）土拨鼠血浆、一种K(ATP)通道阻滞剂或阿片拮抗剂进行预处理的功能效应。在复氧期，仅在用HWP预处理的肌束中观察到明显更大的力量恢复；这种反应被纳洛酮阻断（P < 0.05）。我们得出结论，HIT预处理可用于保护非冬眠动物的骨骼肌免受缺氧/再灌注损伤；它有可能被用于预防需要缺血的外科手术过程中的损伤。
