摘要
目的通过建立在体大鼠肺缺血再灌注损伤模型,研究米力农雾化吸入对缺血再灌注肺损伤的影响,并对其机制进行探讨。方法 30只Sprague-Dawley大鼠随机分成3组,每组10只。假手术组(Ⅰ组):开胸游离左肺门,未行肺门阻断。缺血再灌注组(Ⅱ组):阻断肺门45min后开放再灌注2h。吸入米力农-缺血再灌注组(Ⅲ组):0.4mg/mL米力农吸入30min后,肺门阻断45min,肺门开放后继续吸入2h。再灌注2h后行动脉血气分析计算氧合指数[动脉氧分压(paO2)/吸入氧浓度(FiO2)]及肺内分流率(Qs/Qt),检测肺湿干比(W/D)、丙二醛(MDA)、髓过氧化物酶(MPO)、诱导型一氧化氮合酶(iNOS)和内皮源性一氧化氮合酶(eNOS)水平,并对左肺组织进行病理学检查。结果Ⅱ组的paO2/FiO2显著低于Ⅰ组(P<0.05),Ⅲ组显著高于Ⅱ组(P<0.05);Ⅱ组Qs/Qt、W/D均显著高于Ⅰ组(P值均<0.05),Ⅲ组显著低于Ⅱ组(P值均<0.05)。Ⅱ组MDA水平、MPO及iNOS活性均显著高于Ⅰ组(P值均<0.05),Ⅲ组显著低于Ⅱ组(P值均<0.05);Ⅱ组eNOS显著低于Ⅰ组(P<0.05),Ⅲ组显著高于Ⅱ组(P<0.05)。病理学结果显示,3组动物肺组织结构基本正常,Ⅰ组和Ⅲ组无充血,Ⅱ组肺组织充血明显且炎性细胞较其他两组明显增多。结论雾化吸入米力农可减轻肺组织的缺血再灌注损伤。其机制可能与增加eNOS活性,降低iNOS活性,减少肺组织内炎性细胞浸润以及减轻内皮细胞功能紊乱有关。
Objective To investigate the effect of inhaled milrinone on experimental lung ischemia reperfusion injury（IRI）in rats and the related mechanism.Methods Thirty Sprague-Dawley rats were evenly randomized into 3 groups：Sham（group Ⅰ）,thoracotomy without pulmonary hilum occlusion;IRI（group Ⅱ）,occlusion of the left pulmonary hilum for 45 min,followed by 2 h reperfusion;and milrinone inhalation（group Ⅲ）,0.4 mg/mL milrinone inhaled for 30 min before IR procedure.Artery blood gas analysis was done before ischemia and 2 h after reperfusion for measurement of paO2/FiO2 and Qs/Qt.The ratio of wet to dry lung weight（W/D）,concentration of malondialdehyde（MDA）,myeloperoxidase（MPO）,inducible nitric oxide synthase（iNOS）,and endothelial NOS（eNOS）were detected by biochemical methods,and histopathology examination of left lung was also assessed 2h after reperfusion.Results The values of paO2/FiO2 in group Ⅰ and group Ⅲ were significantly higher than that of group Ⅱ（P〈0.05）.The lung wet/dry ratio and Qs/Qt in group I were significantly lower than those in group Ⅱ（P〈0.05）,and those in group Ⅲ were significantly than those in group Ⅱ（P〈0.05）.The MDA content,MPO and iNOS activities in group Ⅰ and group Ⅲ were significantly lower than those in group Ⅱ（P〈0.05）,but the eNOS activity was higher than that in group Ⅱ（P〈0.05）.Pathologic examination displayed basically normal lung structure in all the 3 groups,and no hyperemia was found in group Ⅰ and group Ⅲ.Group Ⅱ had obvious hyperemia and more inflammatory cells than group Ⅰ and Ⅲ.Conclusion Inhalation of milrinone can relieve ischemia-reperfusion injury of the lung tissues,which might be associated with increased eNOS activity,decreased iNOS activity,reduced infiltration of the lung inflammatory cells,and improved endothelial cell dysfunction.（Shanghai Med J,2010,33：712-715）
出处
《上海医学》
CAS
CSCD
北大核心
2010年第8期712-715,I0002,共5页
Shanghai Medical Journal
基金
上海市卫生局青年基金资助项目(2007Y28)
