急性美沙酮治疗可通过δ -阿片受体减少再灌注期间大鼠心肌梗死面积。

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Gross ER, Hsu AK, Gross GJ

急性美沙酮治疗可通过δ -阿片受体减少再灌注期间大鼠心肌梗死面积。

中华麻醉学杂志2009 11月;109(5):1395-402。doi: 10.1213 / ANE.0b013e3181b92201。

PubMed ID

19843777 (PubMed视图

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摘要

背景:美沙酮是一种阿片类激动剂，通常用于管理急性和慢性疼痛。我们试图确定美沙酮与吗啡相比是否依赖于减少心肌梗死面积(IS)，其机制是否由δ阿片受体介导。此外，我们还研究了心肌IS减少是否与美沙酮给药时间或诱导缺血时间有关。方法:手术固定后，我们将雄性sd大鼠分为3组。第一组分为组，缺血前30min给予美沙酮(0.03-3 mg/kg)、吗啡(0.03-3 mg/kg)、水(安慰剂)。第一组动物在美沙酮(0.3 mg/kg)、吗啡(0.3 mg/kg)或安慰剂之前，也接受delta-阿片拮抗剂纳曲吲哚(5 mg/kg)。第二组动物分为两组，分别于再灌注前5 min和再灌注后10 s给予美沙酮0.3 mg/kg。两组动物均采用冠状动脉左前降支阻断心肌缺血30min，再灌注2h。第三组动物在再灌注前5 min给予安慰剂、美沙酮(0.3 mg/kg)或吗啡(0.3 mg/kg)，左冠状动脉前降支阻断缺血45 min，再灌注2 h。心肌IS通过三苯四唑氯化铵(triphenyltetrazium chloride)染色心肌组织来评估，并表示为危险区域的百分比(mean +/- sem)。 RESULTS: Methadone or morphine administered before ischemia reduced myocardial IS. The greatest effect was achieved at a dose of 0.3 mg/kg (methadone, 46% +/- 1%, P < 0.001 and morphine, 47% +/- 1%, P < 0.001 versus placebo, 61% +/- 1%, respectively). Naltrindole (5 mg/kg) blocked methadone-induced (0.3 mg/kg) and morphine-induced (0.3 mg/kg) cardioprotection (naltrindole + methadone, 58% +/- 1%, P < 0.001 versus methadone; and naltrindole + morphine, 58 +/- 1%, P < 0.001 versus morphine). Methadone (0.3 mg/kg) reduced myocardial IS when given 5 min before reperfusion (46% +/- 1%, P < 0.001 versus placebo) but not 10 s after reperfusion (60% +/- 1%, P = 0.675 versus placebo). No significant myocardial IS differences were seen for placebo when comparing the 45-min ischemia group (64% +/- 1%) with the 30-min ischemia group (60% +/- 1%, P = 0.069). The longer ischemia time of 45 min abrogated methadone-induced IS reduction (64% +/- 2%, P = 0.867 versus 45-min ischemia placebo group) and morphine-induced IS reduction (65% +/- 1%, P = 0.836 versus 45-min ischemia placebo group). CONCLUSIONS: These findings demonstrate that methadone and morphine produce similar myocardial IS-sparing effects that are delta-opioid receptor mediated and that are dependent on the duration of myocardial ischemia.

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药物靶点

药物	目标	种类	生物	药理作用	行动
美沙酮	delta型阿片受体	蛋白质	人类	是的	受体激动剂	细节