地佐辛后处理对大鼠肠缺血再灌注致急性肺损伤的影响

Effect of dezocine post conditioning on acute lung injury induced by intestinal ischemia-reperfusion in rats

目的探讨地佐辛后处理对大鼠肠缺血再灌注所致急性肺损伤的影响以及可能的机制。方法选取健康成年雄性SD大鼠32只,采用随机数字表法分为4组:CON组为假手术组;II/R组制备肠缺血再灌注模型;Dez组于缺血1 h经股静脉注射地佐辛3 mg 0.6 m L,再灌注1 h;5-HD组于缺血前30 min腹腔注射5-羟基葵酸钠10 mg/kg,随后制备肠缺血再灌注模型,后续处理同Dez组。再灌注1 h即刻,取部分肠组织,观察肠粘膜形态并进行肠粘膜损伤评分;取左肺组织,观察肺组织形态并进行肺损伤评分;取右肺组织测定丙二醛MDA的含量、超氧化物岐化酶SOD活性及髓过氧化物酶MPO的活性,取动脉血检测血清中TNF-a和IL-6的水平。结果地佐辛后处理能减轻肠缺血再灌注引起的远隔脏器肺的损伤,降低肠粘膜损伤评分、肺损伤评分,使肺组织丙二醛MDA的含量降低,超氧化物岐化酶SOD活性上升,髓过氧化物酶MPO的活性下降,血清TNF-a和IL-6的浓度明显下降。使用线粒体ATP敏感钾通道抑制剂5-羟基葵酸钠处理后可以减弱地佐辛对肺损伤的保护效应。结论地佐辛后处理可改善大鼠肠缺血再灌注对远隔脏器肺的损害,激活线粒体ATP敏感钾通道可能是保护机制之一。

Objective To explore dezoeine post conditioning on acute lung injury induced by intestinal isehemia and reperfusion induced in rats. Methods According to the random number seed, the healthy male SD rats were randomly divided into 4 groups ： Rats in Control group （CON group） were subjected to separate the superior mesenterie artery without being obstructed. Rats in intestinal isehemia-reperfusion group （II/R group） were set intestinal isehemia- reperfusion model and administered saline 0.6 mL intravenously after occlusion. In dezocine post conditioning group （ Dez group） rats were administered dezocine 0.6 mL 3 mg intravenously after occlusion. In 5-hydroxydecanoate sodium group （5- HD group） rats were administered 5-hydroxydecanoate sodium （10 mg/kg） by peritoneal injection 30min before occlusion then operated as group Dez. The animals were killed at 1 h of reperfusion with the intestinal tissue removed to calculate the index of quantitative assessment of intestinal mucous membrane injury. Tissues of left lung were obtained for observation ofhistopathology with light microscope and the index of quantitative assessment of histologic lung injury was calculated. The concentrations of malondialdehyde （MI）A） , superoxlde dismutase （SOD） activation and myeloperoxidase level in each group were detected via tissues of left lung. The concentrations of TNF-a and IL-6 were also examined. Results Acute lung injury induced by intestinal ischemia and reperfusion induced in rats was improved by dezocine post conditioning. Chiu score, lung injure score, malondialdehyde （MDA） content, myeloperoxidase（MPO） level and the concentrations of TNF-a and IL-6 were descended while superoxide dismutase （SOD） activation was rised. The protective effects of dezocine post conditioning were attenuated by injecting S-hydroxydecanoate sodium via peritoneal cavity which was a selective mitochondrial ATP-sensitive potassium channel antagonist. Conclusions Dezocine post-conditioning protects against lung injury induced by intestinal ischemia-reperfusion in rats. One of the protective effects may be related to opening mitochondrial ATP-sensitive potassium channel.