吗啡预处理对兔肺缺血再灌注损伤的保护作用

Protective effects of morphine preconditioning on the lungs against ischemia-reperfusion injury in rabbits

目的探讨吗啡预处理对兔肺缺血再灌注损伤的保护作用及其可能机制。方法24 只日本大耳白兔随机分为3组(n=8):假手术组(S组)、缺血再灌注损伤组(I-R组)和吗啡预处理组(M组)。I-R、M组通过阻断左肺门2 h及再灌注2 h造成肺缺血再灌注损伤模型,M组阻断左肺门前30 min经肺动脉注入吗啡4 mg/kg,I-R组注射等量生理盐水。S组手术操作同其他两组,但不行左肺门阻断及给药。分别在阻断左肺门前(缺血前)、再灌注5、30、60、90及120 min时测定动脉血氧分压(PaO2)、平均肺动脉压(MPAP)和气道峰压(PIP),并在缺血前、再灌注60、120min时测定血浆内皮素-1 (ET-1)浓度,实验结束时测定支气管肺泡灌洗液(BALF)中性粒细胞百分比及肺湿干重比(W/D),并行肺组织病理学检查。结果与S组比较,I-R、M组再灌注各时点PaO2下降,I-R组再灌注30-120 min 时MPAP升高,I-R、M组再灌注60-120 min时PIP升高(P<0.05);与I-R组比较,M组再灌注60-120 min时MPAP、PIP降低,PaO2升高(P<0.05)。再灌注60、120min时I-R组ET-1浓度高于M、S组(P< 0.05),M组与S组比较差异无统计学意义(P>0.05)。M组BALF中性粒细胞百分比和W/D高于S 组,低于I-R组(P<0.01)。结论吗啡4mg/kg预处理对兔肺缺血再灌注损伤具有一定的保护作用, 其机制可能与降低血浆ET-1浓度及抑制中性粒细胞功能有关。

Objective To investigate the protective effects of morphine preconditioning on the lungs against ischemia-reperfusion （I/R） injury and the possible mechanisms. Methods Twenty-four Japanese long-ear white rabbits weighting 2.5-3.0 kg were used in this study. The animals were anesthetized with intramuscular atropine 0.5 mg and intravenous 3 % pentobarbital 30 mg·kg^-1 , tracheostomized and mechanically ventilated （VT 10 ml·kg^-1 , RR 30 bpm, FiO2 100%, PEEP 1 cm H2O）. Right carotid artery was cannulated for BP monitoring and blood sampling. An elastic band was placed around the hilum of left lung via thoracotomy to perform lung ischemia. Body temperature was maintained at 36-38℃ （rectal）. The animals were randomly allocated to one of 3 groups （ n = 8 each） ： （1） Sham group; （2） I/R group was subjected to 2 h in situ left hilar occlusion followed by 2 h reperfusion and （3） morphine preconditioning group received morphine 4 mg·kg^-1 via pulmonary artery 30 min before I/R. Mean pulmonary artery pressure （MPAP） and peak inspiratory pressure （PIP） were monitored and recorded. Arterial blood samples were taken before occlusion of lung hilum （baseline） and at 5, 30, 60, 90 and 120 min of reperfusion for blood gas analysis, and determination of plasma endothelin-1 concentration. The animals were killed at the end of 120 min reperfusion. The lungs were removed for determination of lung water content （W/ D ratio ） , percentage of neutrophils in the broncho-alveolar lavage fluid （ BALF ） and microscopic examination. Results MPAP and PIP were significantly lower while PaO2 was significantly higher at 30, 60, 90 and 120 min of reperfusion in morphine preconditioning group than in I/R group. Plasma endothelin-1 concentration was significantly lower at 60 and 120 min of reperfusion in morphine preconditioning group than in I/R group （ P 〈0.05）. W/D ratio and percentage of neutrophils in BALF were significantly lower in morphine preconditioning group than in I/R group （ P 〈 0.01）. Conclusion Morphine preconditioning attenuates I/R injury to the lungs. Decrease in plasma endothelin-1 concentration after reperfusion and neutrophil function suppression may be involved in the mechanism.