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离体灌注模型氢气预处理对心脏死亡器官捐献移植供体肺组织的保护作用

Protective effects of hydrogen preconditioning in an ex vivo perfusion model on lung tissue from organ donation donors after cardiac death

    摘要
  • 摘要:
      目的  探讨离体灌注模型氢气预处理对心脏死亡器官捐献（DCD）移植供体肺组织的保护作用。
      方法  选用新西兰大耳白兔18只，构建离体肺灌注（EVLP）模型，采用空气或含2%氢气的空气进行通气，并对动脉和气道压力连续监测；每小时取灌注液以检查氧合情况。EVLP模型建立后，将肺移植物正位移植到同龄大耳白兔体内，并检查肺功能。
      结果  EVLP灌注4 h时，2组氧合指数pa（O2）/FiO2、肺血管阻力（PVR）和动态肺顺应性比较，差异有统计学意义（P < 0.05）。EVLP期间，氢气组肺移植物白细胞介素（IL）-6、IL-1β、肿瘤坏死因子-α（TNF-α）和缺氧诱导因子-1α（HIF-1α）的mRNA表达水平高于假手术组，但低于对照组，差异有统计学意义（P < 0.05）。2组EVLP灌注4 h时葡萄糖消耗量较1、2、3 h时降低，差异有统计学意义（P < 0.05）；EVLP灌注4 h时，对照组乳酸水平较1、2、3 h时升高，差异有统计学意义（P < 0.05）；氢气组1、2、3、4 h时乳酸水平低于对照组，差异有统计学意义（P < 0.05）。EVLP 4 h后，对照组、氢气组肺组织中线粒体复合物Ⅰ酶活性较假手术组降低，线粒体复合物Ⅱ、Ⅳ活性、ATP水平较对照组、假手术组均升高，差异有统计学意义（P < 0.05）。EVLP期间，氢气组血红素氧合酶（HO）-1、过氧化物酶体增殖物激活受体γ辅激活因子（PGC）-1和核呼吸因子-1（NRF-1）的mRNA表达水平均高于对照组、假手术组，差异有统计学意义（P < 0.05）。
      结论  EVLP肺移植表现出显著的促炎变化和代谢谱受损。氢气预处理肺移植物可明显减轻促炎反应，促进肺移植整个过程中肺内线粒体的生物合成，并对移植肺功能起到较好的保护作用。

     

    Abstract:
      Objective  To investigate the protective effect of hydrogen preconditioning in an ex vivo perfusion model on lung tissue from organ donation donors after cardiac death (DCD).
      Methods  Eighteen New Zealand white rabbits were selected to construct ex vivo lung perfusion (EVLP) model. Air or air containing 2% hydrogen was used for ventilation, and arterial and airway pressure was monitored continuously. The infusion was sampled hourly to check for oxygenation. After EVLP, lung grafts were transplanted into large-eared rabbits of the same age in positive position, and lung function was examined.
      Results  There were statistically significant differences in oxygenation indexpa(O2)/FiO2, pulmonary vascular resistance (PVR) and dynamic lung compliance between the two groups at 4 h after EVLP perfusion (P < 0.05). During EVLP, the mRNA expression levels of interleukin (IL-6), IL-1β, tumor necrosis factor-α (TNF-α) and hypoxia-inducible factor-1 α (HIF-1α) in lung grafts in the hydrogen group were higher than those in the sham surgery group, but were lower than those in the control group (P < 0.05). Compared with 1, 2 and 3 h after EVLP perfusion, glucose consumption in both groups was decreased at 4 h (P < 0.05). The level of lactic acid in the control group at 4 h after EVLP was higher than that at 1, 2 and 3 h (P < 0.05). The lactic acid levels at 1, 2, 3 and 4 h in the hydrogen group were lower than those in the control group(P < 0.05). After EVLP for 4 h, the mitochondrial complex Ⅰ enzyme activity in the lung tissues of the control group and the hydrogen group was lower than that of the sham operation group, while the mitochondrial complex Ⅱ and Ⅳ activities and ATP levels in the hydrogen group were higher than those in the control group and the sham operation group (P < 0.05). During EVLP, the mRNA expression levels of heme oxygenase (HO) -1, peroxisome proliferator-activated receptor γ co-activator 1 (PGC-1) and nuclear respiratory factor-1 (NRF-1) in the hydrogen group were higher than those in control group and the sham operation group (P < 0.05).
      Conclusion  EVLP lung transplantation shows significant pro-inflammatory changes and impaired metabolic profile. Hydrogen pretreated lung graft can significantly reduce the proinflammatory reactions, promote the biogenesis of mitochondria in the lung during the whole process of lung transplantation, and play a better role in protecting the function of the transplanted lung.

     

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