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目的探讨金纳多对肺移植术供体肺缺血再灌注损伤的保护作用及机制。方法建立模拟的兔肺自体原位移植模型。分为单纯缺血再灌注(I/R)组(n=6),改良LPD液灌注(LPD)组(n=6)和金纳多治疗(LPD+E)组(n=6)。监测氧分压(PaO2)、血清肿瘤坏死因子(TNF-α)的变化,左肺作肺组织干/湿重比值(D/W)、丙二醛(MDA)含量、髓过氧化物酶(MPO)活力的测定,并在光镜下观察肺组织病理变化。结果(1)3组再灌注后15、60和90min的PaO2均有明显的下降,但LPD+E组明显好于I/R组(各时点分别为212.2mmHg±53.9mmHgvs122.5mmHg±20.7mmHg,240.5mmHg±52.5mmHgvs64.5mmHg±5.6mmHg,236.5mmHg±51.1mmHgvs100.0mmHg±8.6mmHg,P<0.01),LPD组与LPD+E组相比差异无统计学意义。(2)I/R组和LPD组再灌注后各时点及LPD+E组再灌注后60min、90min后TNF-α水平高于缺血前,但LPD+E组明显低于其余两组(分别为53.0ng/L±6.2ng/Lvs98.5ng/L±2.8ng/L、86.9ng/L±3.5ng/L,56.5ng/L±6.3ng/Lvs103.7ng/L±4.4ng/L、90.2ng/L±2.4ng/L,P<0.05)。(3)I/R组、LPD组和LPD+E组肺组织MDA含量分别为12.4nmol/mg±1.1nmol/mg、9.9nmol/mg±0.9nmol/mg、6.6nmol/mg±0.7nmol/mg,MPO活力分别为14.85U/g±1.40U/g、12.81U/g±1.04U/g、10.38U/g±1.07U/g,各组间比较P<0.01。(4)肺组织D/W比值:I/R组、LPD组和LPD+E组分别为0.1309±0.0122、0.1550±0.0096、0.1775±0.0073,各组间比较P<0.01。(5)病理学改变:I/R组肺组织损伤严重,肺泡间隔大量炎症细胞浸润,肺泡腔内炎症细胞聚集、炎性液体渗出,可见片状出血,LPD+E组病理改变最为轻微,炎症细胞浸润、炎性渗液不显著。结论金纳多对兔移植肺缺血再灌注损伤具有明显的保护作用,其作用机制可能通过与抗氧化、抑制中性粒细胞聚集和炎症因子TNF-α的释放有关。
Objective To investigate the protective effect and mechanism of Ginaton on pulmonary ischemia-reperfusion injury in donor lung transplantation. Methods A model rabbit model of orthotopic autotransplantation was established. They were divided into simple ischemia-reperfusion (I/R) group (n=6), modified LPD fluid perfusion (LPD) group (n=6) and Ginaton-treated (LPD+E) group (n=6). The changes of oxygen partial pressure (PaO2) and serum tumor necrosis factor (TNF-α) were monitored. The ratio of lung dry/wet weight (D/W) in the left lung, malondialdehyde (MDA) content, and myeloperoxidase ( Determine the vitality of MPO) and observe the pathological changes of lung tissue under light microscope. Results (1) The PaO2 at 15th, 60th, and 90th minutes after reperfusion in all three groups decreased significantly, but the LPD+E group was significantly better than the I/R group (212.2mmHg±53.9mmHgvs122.5mmHg±20.7mmHg at each time point). , 240.5mmHg ± 52.5mmHgvs64.5mmHg ± 5.6mmHg, 236.5mmHg ± 51.1mmHgvs100.0mmHg ± 8.6mmHg, P <0.01), LPD group and LPD + E group compared the difference was not statistically significant. (2) The levels of TNF-α were higher in I/R group and LPD group than those in other groups after reperfusion and in 60 minutes and 90 minutes after reperfusion in LPD+E group. They were 53.0 ng/L ± 6.2 ng/L vs 98.5 ng/L ± 2.8 ng/L, 86.9 ng/L ± 3.5 ng/L, 56.5 ng/L ± 6.3 ng/L vs 103.7 ng/L ± 4.4 ng/L, respectively. 90.2 ng/L ± 2.4 ng/L, P < 0.05). (3) The MDA contents in lung tissues of I/R group, LPD group and LPD+E group were 12.4 nmol/mg±1.1 nmol/mg, 9.9 nmol/mg±0.9 nmol/mg, and 6.6 nmol/mg±0.7 nmol/mg, respectively. The MPO motility was 14.85 U/g±1.40 U/g, 12.81 U/g±1.04 U/g, and 10.38 U/g±1.07 U/g, respectively. P<0.01 for each group. (4) The lung tissue D/W ratios were 0.1309±0.0122, 0.1550±0.0096, and 0.1775±0.0073 in I/R group, LPD group, and LPD+E group, respectively, P<0.01 for each group. (5) Pathological changes: In the I/R group, the lung tissue was severely damaged, a large number of inflammatory cells were infiltrated in the alveolar septum, the inflammatory cells in the alveolar space were aggregated, and the inflammatory fluid was oozing. The flaky hemorrhage was seen. The pathological changes in the LPD+E group were the slightest. Inflammation cell infiltration and inflammatory exudate were not significant. Conclusion Ginaton has obvious protective effect on lung ischemia-reperfusion injury in rabbits, and its mechanism may be related to anti-oxidation, inhibition of neutrophil accumulation and release of TNF-α.