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2012年第2期
米力农雾化吸入对大鼠肺移植后肺缺血再灌注损伤的影响
Effect of inhaled milrinone on experimental lung ischemia reperfusion injury in a rat model of lung transplantation
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DOI:
作者:
卫炯琳,吴镜湘,朱宏伟,徐美英
WEI Jionglin, WU Jingxiang, ZHU Hongwei, XU Meiyin
作者单位:
上海交通大学附属上海市胸科医院麻醉科
Department of Anesthesiology,Shanghai Chest Hospital,Shanghai Jiaotong University
关键词:
米力农;雾化吸入;肺移植;缺血再灌注损伤;大鼠
Milrinone; Inhalation ;Lung ischemia reperfusion injury; Lung transplantation; Rats
摘要:
目的 观察米力农雾化吸入对大鼠原位肺移植后肺缺血再灌注损伤的影响,并探讨可能的机制。方法 30只SD雄性大鼠随机分成3组,每组10只。假手术组(Ⅰ组):开胸游离左肺门,未行肺移植;肺移植组(Ⅱ组):左肺移植后开放再灌注2h;肺移植后-吸入米力农治疗组(Ⅲ组):左肺移植后再灌注开始同时0.4mg/ml米力农雾化吸入2h。再灌注2h后行动脉血气分析计算PaO2/FiO2及Qs /Qt,检测肺湿干比(W/D),髓过氧化物酶(MPO) 和丙二醛(MDA)含量以及诱导型一氧化氮合酶(iNOS)、内皮源性一氧化氮合酶(eNOS)含量,并且对左肺组织进行病理学检查。结果Ⅰ组和Ⅲ组的PaO2/FiO2高于Ⅱ组(P<0.05),Qs/Qt和W/D低于Ⅱ组(P<0.05);Ⅰ组和Ⅲ组的MDA含量、MPO及iNOS活性低于Ⅱ组(P<0.05),Ⅰ组和Ⅲ组的eNOS活性高于Ⅱ组(P<0.05);病理学结果显示:与Ⅰ组比较,Ⅱ组和Ⅲ组左肺组织充血明显且炎症细胞明显增多;而Ⅲ组较Ⅱ组左肺炎症细胞明显减少。结论 雾化吸入米力农的使用可减轻大鼠肺移植后肺组织的缺血再灌注损伤, 可能的作用机制与增加eNOS活性,降低iNOS的活性,减少肺组织内炎性细胞的浸润,减轻内皮细胞功能的紊乱有关。
Objective To investigate the effect and the related mechanism of inhaled milrinone on experimental lung ischemia reperfusion injury(IRI)in a rat model of lung transplantation. Methods Thirty male SD rats were evenly randomized into 3 groups:sham operation group(group Ⅰ);lung transplantation group(group Ⅱ)and lung transplantation+milrinone group(group Ⅲ). In groupⅡ and Ⅲ orthotopic left lung transplantation was performed followed by 2 hours reperfusion. In group Ⅲ 0.4 mg/ml milrinone inhaled for 2 hours during the reperfusion. 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 groupⅠand 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 lower than those in group Ⅱ(P〈0.05).The MDA content, MPO and iNOS activities in groupⅠand 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 groupⅠand group Ⅲ.Group Ⅱ had obvious hyperemia and more inflammatory cells than group Ⅰ and Ⅲ. Conclusion Inhalation of milrinone can reduce ischemia-reperfusion injury to the transplanted donor lungs, which might be associated with increased eNOS activity, decreased iNOS activity, relieved infiltration of the lung inflammatory cells, and improved endothelial cell dysfunction.