Cardiology Research Institute, Tomsk National Research Medical Centre, Russian Academy of Sciences, Tomsk, Russia.
Bull Exp Biol Med. 2021 Mar;170(5):604-607. doi: 10.1007/s10517-021-05115-5. Epub 2021 Apr 1.
The study examined the effects of δ-opioid receptor (OR) agonists on infarct size on cardiac ischemia (45 min) and reperfusion (120 min) in vivo model in rats narcotized with α-chloralose. The OR agonists were injected intravenously 5 min prior to reperfusion, OR antagonists were administered 10 min before reperfusion. A selective δ-OR agonist BW373U86 (1 mg/kg) reduced the infarct size/area at risk ratio. A selective δ-OR agonist DPDPE injected in the doses of 0.1 or 0.969 mg/kg produced no effect on infarct size. The selective δ-OR agonist deltorphin II (0.12 mg/kg) reduced infarct size/area at risk ratio by 2 times. The δ-OR agonist p-Cl-Phe-DPDPE (1 mg/kg) reduced infarct size/area at risk ratio by 40%. Naltrexone and naloxone methiodide, the peripheral OR antagonists, and selective δ-OR antagonist naltriben prevented the infarct size limiting effect of deltorphin II. Therefore, activation of peripheral δ-OR enhanced cardiac resistance against toxic action of reperfusion. During reperfusion, deltorphin II demonstrated the most pronounced cardioprotective activity.
该研究在α-氯醛糖麻醉大鼠的体内模型中,考察了 δ-阿片受体(OR)激动剂对缺血(45 分钟)和再灌注(120 分钟)期间梗死面积的影响。OR 激动剂在再灌注前 5 分钟静脉注射,OR 拮抗剂在再灌注前 10 分钟给药。选择性 δ-OR 激动剂 BW373U86(1mg/kg)减少了梗死面积/危险区的比值。选择性 δ-OR 激动剂 DPDPE 以 0.1 或 0.969mg/kg 的剂量注射对梗死面积没有影响。选择性 δ-OR 激动剂 deltorphin II(0.12mg/kg)使梗死面积/危险区的比值降低了 2 倍。δ-OR 激动剂 p-Cl-Phe-DPDPE(1mg/kg)使梗死面积/危险区的比值降低了 40%。外周 OR 拮抗剂纳曲酮和纳洛酮甲碘化物以及选择性 δ-OR 拮抗剂naltriben 预防了 deltorphin II 的梗死面积限制作用。因此,外周 δ-OR 的激活增强了心脏对再灌注毒性作用的抵抗力。在再灌注期间,deltorphin II 表现出最明显的心脏保护活性。