炎症细胞对犬肺移植早期再灌注损伤的影响

Influence of inflammatory cells on early-stage reperfusion injury of canine lung allograft

目的:探讨在移植肺早期再灌注损伤中供肺巨噬细胞和受者循环中性粒细胞的作用以及二者间的相互作用。方法:20对身长、体质量匹配的本地成年杂犬随机平均分配到4组:对照组(C组)、去白细胞再灌注组(D组)、巨噬细胞抑制组(M组)和去白+巨噬细胞抑制组(DM组),由同一外科医生连续施行20次左肺移植手术。M和DM组供者在术前24h静注巨噬细胞抑制剂三氯化钆14mg/kg,D和DM组受者用采自供者下腔静脉的去白细胞血完成前10min再灌注,此外所有实验过程相同。所有移植肺经历2h的再灌注。结果:与C、D组相比,抑制巨噬细胞使M、DM组再灌注30min后的PO_2/FiO_2和平均肺动脉压(mPAP)持续改善,再灌注120min的丙二醛、湿/干比等肺再灌注损伤指标也显著改善(P<0.05)。尽管起始去白再灌注显著减轻了再灌注120min的白细胞滞留(髓过氧化酶),但对移植肺再灌注损伤无显著影响。去白细胞和抑制巨噬细胞在移植肺氧合、mPAP、湿/干比、丙二醛及髓过氧化酶活性方面没有显著的交互作用。结论:再灌注2h内能使移植肺再灌注损伤加剧的炎症细胞是供者肺泡巨噬细胞而非受者循环中性粒细胞,且未发现二者存在交互作用。

Objective： To investigate the roles of donor alveolar macrophages and the recipient circulating neutrophils in early-stage reperfusion injury of lung allograft,and to study the interaction between the 2 kinds of cells. Methods： Twenty pairs of size- and weight-matched adult mongrel dogs were randomly assigned to 4 groups： C （control）, D （leukocyte-depleted blood reperfusion）,M （macrophage inhibition） and DM （leukocyte-depleted plus macrophage inhibition）. The 20 cases of left lung transplantations were performed by the same surgeon. All procedures were identical,except that the donors in Group M and DM received the macrophage inhibitor gadolinium chloride （14 mg/kg） intravenously 24 h before operation,and that the recipients in Group D and DM underwent initial 10 min reperfusion with leukocyte-depleted blood collected from donors＇ inferior vena cava. All lung allografts were reperfused for 2 h. Results： Compared with Group D and C, macrophage inhibition ameliorated PO2/FiO2 and mean pulmonary arterial pressure （mPAP） consistently after 30 min reperfusion in Group M and DM; the parameters of lung reperfusion injury （malonaldehyde activity,wet/dry ratio） at 120 min after reperfusion were also significantly improved （P〈0.05）. Initial leukocyte-depleted reperfusion had no remarkable influence on allograft reperfusion injury, although it reduced pulmonary leukostasis （myeloperoxidase activity） significantly at 120 min after reperfusion. There were no significant interactions between leukocyte-depletion and macrophage inhibition in oxygenation, mPAP, wet/dry ratio, malonaldehyde and myeloperoxidase activity. Conclusion： It is the donor alveolar macrophages,not the recipient circulating neutrophils that canaggravate the inflammatory cascade in lung allografts during 2 h after reperfusion and no interaction is detected between them.