脑腓肽复合山莨菪碱预处理对猪体外循环时肺缺血再灌注损伤的影响

Effects of preconditioning with enkephalin and anisodamine on pulmonary ischemia-reperfusion injury during cardiopulmonary bypass in swine

目的探讨δ阿片受体激动剂脑腓肽复合M受体拮抗剂山莨菪碱预处理对猪体外循环（CPB）时肺缺血再灌注损伤的影响。方法雄性健康白猪14头,3～4月龄,体重30～35 kg,随机分为2组（n=7）：对照组和预处理组。对照组给予常规CPB;预处理组CPB前1 h静脉注射脑腓肽和山莨菪碱各1mg/kg。2组主动脉阻断同时灌注改良St.Thomas停搏液。心脏停搏缺血60 min后开放主动脉再灌注缺血心肌,撤出CPB后1 h处死动物。于CPB前10 min、再灌注10、30、60 min时采集动脉血,测定丙二醛（MDA）浓度,并行动脉血气分析。于CPB前10 min和再灌注60 min时取肺组织,计算肺组织湿/干重（W/D）;光镜下观察肺泡损伤程度（LTD）;透射电镜下观察肺组织超微结构。结果与对照组比较,预处理组再灌注期间MDA浓度、W/D和LTD均降低,PaO2升高（P〈0.05或0.01）。电镜下预处理组较对照组的肺组织超微结构损伤程度轻。结论脑腓肽复合山莨菪碱预处理可减轻猪体外循环时肺缺血再灌注损伤。

Objective To investigate the effects of preconditioning with δ opioid receptor agonist enkephalin and the muscarine receptor antagonist anisodamine on pulmonary ischemia-reperfusion （I/R） injury during cardiopulmonary bypass （CPB） in swine. Methods Fourteen 3-4 month old swines weighing 30-35 kg were randomly divided into 2 groups （n = 7 each）： control group （C） and preconditioning group （P） . Group P received enkephalin 1 mg/kg and anisodamine 1 mg/kg i.v. 1 h before CPB. The animals were anesthetized with balanced propofol anesthesia. CPB was instituted routinely and the modified St.Thomas cold cardioplegic solution was administered into the root of aorta. Cardiac arrest was maintained for 60 min. Aorta was then unclamped. The animals were killed at 1 h after discontinuation of CPB. Arterial blood samples were taken 10 min before CPB （baseline） and at 10, 30 and 60 min of lung reperfusion for blood gas analysis and determination of plasma malondialdehyde （MDA） concentration. Lung specimens were taken 10 min before CPB （baseline） and at 60 min of reperfusion for determination of wet/dry lung weight ratio and microscopic examination of the degree of lung damage（LTD）. Results The plasma MDA concentration and W/D lung weight ratio were significantly lower and LTD was significantly less serious in group P than in control group. PaO2 was significantly higher during reperfusion in group P than in control group. Conclusion Preconditioning with enkephalin and anisodamine can protect the lungs against I/R injury during CPB in swine.