金纳多对兔移植肺缺血再灌注损伤保护作用的实验研究

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。

Protective effects of ginaton against ischemia-reperfusion injury on the autograft after lung autotransplantation: experiment with rabbits

OBJECTIVE: To investigate the effects of ginaton against ischemia-reperfusion injury on the autograft after lung autotransplantation. METHODS: Models of lung autotransplantation were established in 18 New Zealand rabbits were established. The 18 rabbits were randomly divided into 3 equal groups: group of simple ischemia-reperfusion (group I/R), undergoing ischemia by blocking the left pulmonary artery for 2 h and then re-perfusion for 90 min; group with perfusion of low potassium dextran solution (group LPD), undergoing perfusion of LSD solution before ischemia; and group with treatment of ginaton (group LPD + E), undergoing intravenous injection of ginaton 15 min before ischemia. Arterial blood samples were collected before ischemia, and 15, 60, and 90 min after re-perfusion to examine the alveolar oxygen pressure (PaO2). Serum tumor necrosis factor-alpha (TNF-alpha) was monitored before ischemia, and 30, 60, and 90 min after re-perfusion. Then the left lungs were taken out to undergo detection of dry/wet ratio (D/W), pathological examination, and contents of myeloperoxidase (MPO) and the malondialdehyde (MDA) in the lung tissues. RESULTS: (1) The PaO2 decreased significantly after reperfusion in all groups. And the PaO2 values at different time points of Group LPD + E were all significantly higher than those of Group I/R (all P < 0.01), however, there were no significant differences between Group LPD and Group LPD + E. (2) The TNF-alpha level after reperfusion increased in Group I/R and Group LPD, while in Group LPD + E it increased only 60 min and 90 min after the reperfusion. The TNF-alpha levels after reperfusion at all time points of Group LPD + E were all significantly lower than those of the other 2 groups (all P < 0.05). (3) The MPO and MDA levels at all time points after re-perfusion of Group LPD + E were all significantly lower than those of the other 2 groups (all P < 0.01). (4) The value of D/W ratio of Group LPD + E was significantly higher than those of the other 2 groups (both P < 0.01). (5) Pathological examination showed that the lung tissue lesion of Group I/R was severe. Interstitial inflammatory cell infiltration, intra-alveolar inflammatory cell aggregation, exudation and even hemorrhage could be observed. The pathological lesion of Group LPD + E was mild, no significant inflammatory cell infiltration or exudation was observed. CONCLUSION: Ginaton provides a protective effect against ischemia-reperfusion injury on the autograft after lung autotransplantation. The mechanism may be related with antioxidation, inhibition of neutrophil aggregation, and TNF-releasing.