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目的:通过应用3种受体拮抗剂来拮抗阿片受体,探讨瑞芬太尼对急性肺损伤保护作用的机制和通路。方法:将48只健康成年雄性新西兰大白兔随机分为6组(每组8只):对照组予0.9%Na Cl 20 ml·h-1静脉泵入;油酸损伤组予油酸1 ml·kg-1以3 ml·min-1静脉泵入;瑞芬太尼组(瑞芬太尼+油酸)予瑞芬太尼0.2μg·kg-1·min–1静脉泵入,15 min后静脉泵注油酸;μ受体拮抗剂组(μ受体拮抗剂甲纳曲酮+瑞芬太尼+油酸)予甲纳曲酮5 mg·kg-1静脉泵入30 min,然后泵入瑞芬太尼和油酸;κ受体拮抗剂组(κ受体拮抗剂Nor-BNI+瑞芬太尼+油酸)予Nor-BNI 5 mg·kg-1静脉泵入30 min,然后泵入瑞芬太尼和油酸;δ受体拮抗剂组(δ受体拮抗剂纳屈吲哚+瑞芬太尼+油酸)予纳屈吲哚5 mg·kg-1静脉泵入30 min,然后泵入瑞芬太尼和油酸。3种受体拮抗剂的瑞芬太尼剂量均为0.2μg·kg·min-1。观察应用瑞芬太尼泵入前和泵入后6 h大白兔的动脉血氧分压(Pa O2)及二氧化碳分压(Pa CO2),测定其肺组织湿重与干重比(W/D),在光镜下观察肺组织损伤程度,并与对照组进行对比。结果:(1)与对照组比较,油酸损伤组Pa O2降低,Pa CO2及肺组织W/D升高(P<0.05)。(2)与油酸损伤组比较,瑞芬太尼组、κ受体拮抗剂组和δ受体拮抗剂组均Pa O2升高,Pa CO2及肺组织W/D降低;μ受体拮抗剂组则差异无显著性。(3)与瑞芬太尼组比较,μ受体拮抗剂组Pa O2降低,Pa CO2及肺组织W/D升高;κ受体拮抗剂组和δ受体拮抗剂组比较则差异无显著性。结论:瑞芬太尼可能是通过μ受体介导减轻了油酸诱发的兔急性肺损伤。
OBJECTIVE: To explore the protective mechanism of remifentanil on acute lung injury by antagonizing opioid receptor by using three kinds of receptor antagonists. Methods: Forty-eight healthy adult male New Zealand white rabbits were randomly divided into 6 groups (8 in each group): the control group was infused intravenously with 0.9% NaCl 20 ml · h-1; the oleic acid injury group was treated with 1 ml of oleic acid kg-1 by 3 ml · min-1 intravenous infusion; remifentanil (remifentanil + oleic acid) was given intravenously to remifentanil 0.2 μg · kg-1 · min-1 for 15 min Intravenous infusion of oleic acid; μ receptor antagonist group (μ receptor antagonist methylnaltrexone + remifentanil + oleic acid) to naltrexone 5 mg · kg-1 intravenously for 30 min, then pumped Remifentanil and oleic acid; κ-receptor antagonist group (Nor-BNI + remifentanil + oleic acid) was intravenously injected into Nor-BNI 5 mg · kg-1 for 30 min and then pumped Remifentanil and oleic acid; δ receptor antagonist group (δ receptor antagonist nyclidine + remifentanil + oleic acid) was intravenously injected with nystokines 5 mg · kg -1 for 30 min, Then pump it into remifentanil and oleic acid. Remifentanil dose of 3 kinds of receptor antagonists were 0.2μg · kg · min-1. The PaO2 and PaCO2 of rabbits before remifentanil injection and 6 h after the infusion of remifentanil were measured. The ratio of wet weight to dry weight (W / D ), The degree of lung injury was observed under light microscope, and compared with the control group. Results: (1) Compared with the control group, PaO2 decreased and PaCO2 and W / D increased in the oleic acid group (P <0.05). (2) Compared with oleic acid injury group, the remifentanil group, κ receptor antagonist group and δ receptor antagonist group were Pa O2 increased, PaCO2 and lung tissue W / D decreased; μ receptor antagonist Group differences were not significant. (3) Compared with remifentanil group, Pa O2 decreased and PaCO2 and W / D increased in μ receptor antagonist group; there was no significant difference between κ receptor antagonist group and δ receptor antagonist group Sex. CONCLUSION: Remifentanil may reduce oleic acid-induced acute lung injury in rabbits through μ-receptor mediated.