西维来司钠对大鼠左单肺移植缺血再灌注损伤的保护作用

Protective Effccts of Sivelestat Sodium on Ischemia-Reperfusion Injury after Rat Left Unilateral Lung Orthotopic Ttransplantation

目的:研究西维来司钠对大鼠单肺移植肺缺血再灌注损伤的保护作用。方法:建立大鼠原位异体左单肺移植模型。雄性SD大鼠60只,随机分2组,每组又分3个亚组(n=6):假手术组、0.9%氯化钠液对照组、西维来司钠组,分别在冷缺血4h后再灌注2h和24h收集标本,测量移植肺氧合指数(PO2/FiO2)、肺损伤病理评分、移植肺湿干重比(W/D)、髓过氧化物酶活性(MPO)、肺组织和血清中丙二醛(MDA)、细胞因子诱导的中性粒细胞趋化因子(CINC)。结果:再灌注2h,假手术组、对照组、西维来司钠组,PO2/FiO2分别为388,179,265;肺损伤病理评分为3.2,6.5,5.0;W/D分别为3.5,5.6,5.2;MPO活性分别为2.3,5.2,4.4U.g-1;MDA肺组织中活性为0.8,2.61.6,血清中活性为2.3,8.1,5.2nmol·mL-1;CINC活性分别为26.4,114.4,19.9pg·mgpro-1。再灌注24h,各组PO2/FiO2分别为403,155,293;肺损伤病理评分为3.7,11.0,6.7;W/D分别为3.7,6.4,5.2;MPO活性分别为2.3,7.2,5.0U·g-1;MDA肺组织中活性为0.7,1.5,1.2nmol·mgpro-1;血清中活性为2.5,5.5,4.6nmol·mL-1;CINC活性分别为29.3,43.1,32.1pg·mgpro-1。结论:西维来司钠改善移植肺的功能,对大鼠单肺移植肺缺血再灌注损伤具有保护作用,其机制与其抑制中性粒细胞活化,抗炎、抗氧化作用有关。

Objective：To investigate the treatment effects of Sivelestat Sodium （SS） on lung function of ischemia-reperfusion injury after rat left unilateral lung orthotopic transplantation. Methods： Rats were subjected to unilateral left lung orthotopie transplantation. A total of 60 male Sprague-Dawley rats were randomly divided two groups, each group was further subdivided into sham, control, SS group （n = 6, per subgroup）, animas were sacrificed at different reperfusion periods of 2 h and 24 h, respectively. Oxygenation indexes, lung injury scores, wet/dry ratio, myeloperoxidase （MPO） activity, Malondialdehyde （MDA） and cytokine-induced neutrophil ehemotactie factor （CINC） in the transplanted lung and serum were measured. Resuits：The values were 388, 179 and 265 for PO2/FiO2 ; 3.2, 6.5 and 5.0 for lung injury pathology score; 3.5, 5.6 and 5.2 for wet-to-dry ratio; 2.3, 5.2, 4.4 for MPO activity, 0.8, 2.6, 1.6 for MDA activity in lung tissue, 2.3, 8.1, 5.2 for MDA in serum, 26.4, 114.4, 19.9 for CINC activity （Sham, control, and SS groups, respectively） at 2 h reperfusion. After 24 h reperfusion, these values were 403, 155 and 293 for PO2/FiO2 ; 3.7, 11.0 and 6.7 for lung injury pathology score; 3.7, 6.4 and 5.2 for wet to-dry ratio; 2,3, 7.2, 5.0 for MPO activity; 0.7, 1.5, 1.2 for MDA activity in lung tissue, 2.5, 5.5, 4.6 for MDA in serum, 29.3, 43.1, 32. 1 for CINC activity. Our data support that IR causes significant lung injury, which can be reduced by SS treatment. Conclusion：Administration of SS attenuated IR injury by inhibiting oxidation, inflammation and neutrophil priming after rat unilateral left lung orthotopic transplantation.