依达拉奉对肺缺血再灌注损伤保护作用的实验研究

Protection of edaravone against lung ischemia reperfusion injury in rabbits

目的:通过建立兔在体肺热缺血再灌注模型,探讨依达拉奉对兔实验性肺缺血再灌注损伤的影响及作用机制。方法:采用兔肺原位热缺血再灌注损伤模型进行研究。24只大白兔随机分为三组:①对照组(C组,n=8),开胸后不阻断肺门,静脉缓慢推注生理盐水5 ml/kg;②缺血再灌注组(I/R组,n=8),左肺接受60 min的缺血,然后接受60 min再灌注,于缺血前5 min静脉缓慢推注生理盐水5 ml/kg;③依达拉奉干预组(E组,n=8),于缺血前5 min静脉缓慢推注依达拉奉10 mg/kg(5 ml/kg),左肺接受60 min的缺血,然后接受60 min再灌注。120 min实验结束时,留取各组动物血液标本,测定血浆丙二醛(MDA)含量及超氧化物歧化酶(SOD)活性;收集支气管肺泡灌洗液(BALF),检测支气管肺泡灌洗液中白细胞计数、中性粒细胞百分比及肺通透性指数;留取肺组织标本,测定肺组织湿、干重量,计算干/湿重比(D/W)及行肺组织病理检查。结果:I/R组血浆丙二醛含量、支气管肺泡灌洗液中蛋白含量、支气管肺泡灌洗液中WBC总数及中性粒细胞百分比明显高于C组及E组(P<0.01),E组与C组比较,无统计学意义(P>0.05);I/R组血浆SOD活性、血清蛋白含量及肺组织干/湿重比(D/W)较C组及E组显著降低(P<0.05),E组与C组比较,无统计学意义(P>0.05);肺通透指数I/R组明显高于E组与C组(P<0.01),E组显著高于C组(P<0.05);肺组织病理显示,E组肺泡内出血、炎性细胞浸润、渗出及间质水肿均较I/R组为轻。结论:依达拉奉通过清除氧自由基、抑制脂质过氧化,对兔肺原位热缺血再灌注损伤有一定保护作用。

Objective： To investigate whether or not edaravone has an effect on reducing lung isehemiarepetfusion injury in rabbits. Methods： Twenty-four rabbits were randomly divided into three groups： ① the control group（group C, n = 8）： received stemotomy only and no ischemia; ② the ischemia/repeffusion group（group I/R, n = 8） ： the left lungs of rabbits were rendered ischemia by ligating the left pulmonary hili for 60 minutes followedby 60 minutes repeffusion; ③ the edaravone group（group E, n = 8） ： the left lungs were rendered ischemia for 60 minutes followed by 60 minutes reperfusion, and 10 mg/kg edaravone was administered intravenously 5 minutes prior to ischemia. Blood MDA and SOD were measured. Protein concentrations, WBC count, and PMN percentage in broncho-alveolar lavage fluid were determined. Samples of left lung tissue were sent for determining the left lung dry-to-wet weight ratio and evaluating the pathologic changes. Results： Blood MDA level, protein concentrations, WBC count and PMN percentage in bronchoalveolar lavage fluid of group I/R were significantly higher than those of group C and group E（ P 〈 0.01 ）, and there was not significant difference between group C and group E （ P 〉 0.05） ; serum SOD activity, serum albumin concentration and left lung dry-to-wet ratio of of group I/R were significantly lower than those of group C and group E（ P 〈 0.05）, and there was not significant difference between group C and group E （ P 〉 0.05） ; the pulmonary permeability index of group I/R was significantly higher than that of group C and group E（ P 〈 0.01 ）; pathologic evaluations revealed mild alterations in alveolar structure, less white blood cell infiltration and less interstitial edema in group E than in group I/R. Conclusions： This study suggests that intravenous edaravone prior to ischemia attenuates the lung ischemia reperfusion injury in rabbits through its radical scavenging and antioxidant action.