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目的:在线粒体水平研究心跳骤停与心肺复苏期间,激动δ阿片受体诱导药物性心肌冬眠保护复苏后心功能的机制。方法:交流电致颤法诱发大鼠心室颤动,8min的室颤后开始包括胸外按压和机械通气的心肺复苏,6min后电击除颤。动物随机分为3组:(1)心肺复苏组;(2)δ阿片受体激动剂组;(3)δ阿片受体拮抗剂+δ阿片受体激动剂组。δ阿片受体拮抗剂在室颤前15min预先给药,δ阿片受体激动剂或者生理盐水在室颤5min时给药。动态监测血流动力学,在复苏成功后6h处死动物电镜观察心肌线粒体损伤情况。结果:δ阿片受体激动剂组复苏后心功能明显改善,δ阿片受体拈抗剂预处理完全取消其保护作用;和心肺复苏组和8阿片受体拮抗剂组相比较,δ阿片受体激动剂组动物心肌的线粒体超微结构的完整性明显保存完好。结论:在心跳骤停与心肺复苏期间激动δ阿片受体诱导药物性心肌冬眠通过保护心肌线粒体超微结构的完整性,从而减轻复苏后心功能损伤。
OBJECTIVE: To study the mechanism of cardiac function induced by agonistic δ-opioid receptor-induced cardiopulmonary hibernation after cardiac arrest and cardiopulmonary resuscitation at the mitochondrial level. Methods: Ventricular fibrillation was induced by AC electrfragmentation in rats. Cardiopulmonary resuscitation including chest compressions and mechanical ventilation was started after ventricular fibrillation (8 min) and was defibrillated after 6 min. The animals were randomly divided into three groups: (1) CPR group; (2) δ opioid receptor agonist group; (3) δ opioid receptor antagonist + δ opioid receptor agonist group. δ opioid receptor antagonist 15 min before the pre-ventricular fibrillation, δ opioid receptor agonist or normal saline at 5 min when administered ventricular fibrillation. Dynamic hemodynamic monitoring was performed, animals were sacrificed at 6 hours after resuscitation to observe myocardial mitochondrial damage. Results: The cardiac function of δ opioid receptor agonist group after resuscitation was significantly improved, and δ opioid receptor antagonist pretreatment completely abolished its protective effect. Compared with CPO group and 8 opioid receptor antagonist group, δ opioid receptor The integrity of the mitochondrial ultrastructure of the cardiac muscle of the agonist group was clearly well preserved. CONCLUSIONS: Activation of δ-opioid receptors induces drug-induced myocardial hibernation during cardiorespiratory arrest and cardiopulmonary resuscitation by protecting the integrity of cardiac myocyte ultrastructure and thereby reducing cardiac function impairment after resuscitation.