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氢气吸入对心脏死亡供体大鼠在热缺血期对肺缺血再灌注损伤的保护作用。

Protective effects of hydrogen inhalation during the warm ischemia phase against lung ischemia-reperfusion injury in rat donors after cardiac death.

机构信息

Department of Anesthesiology, The Second Affiliated Hospital of Harbin Medical University, The Hei Long jiang Province Key Lab of Research on Anesthesiology and Critical Care Medicine, Harbin, China.

Department of Anesthesiology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.

出版信息

Microvasc Res. 2019 Sep;125:103885. doi: 10.1016/j.mvr.2019.103885. Epub 2019 Jun 5.

DOI:10.1016/j.mvr.2019.103885
PMID:31175855
Abstract

BACKGROUND

Successful amelioration of long-term warm ischemia lung injury in donors after cardiac death (DCDs) can remarkably improve outcomes. Hydrogen gas provides potent anti-inflammatory and antioxidant effects against ischemia-reperfusion injury (IRI). This study observed the effects of hydrogen inhalation on lung grafts during the warm ischemia phase in cardiac death donors.

METHODS

After cardiac death, rat donor lungs (n = 8) underwent mechanical ventilation with 40% oxygen plus 60% nitrogen (control group) or 3% hydrogen and 40% oxygen plus 57% nitrogen (hydrogen group) for 2 h during the warm ischemia phase in situ. Then, lung transplantation was performed after 2 h of cold storage and 3 h of recipient reperfusion prior to lung graft assessment. Rats that underwent left thoracotomy without transplantation served as the sham group (n = 8). The results of static compliance and arterial blood gas analysis were assessed in the recipients. The wet-to-dry weight ratio (W/D), inflammation, oxidative stress, cell apoptosis and histologic changes were evaluated after 3 h of reperfusion. Nuclear factor kappa B (NF-κB) protein expression in the graft was analyzed by Western blotting.

RESULTS

Compared with the sham group, lung function, W/D, inflammatory reaction, oxidative stress and histological changes were decreased in both transplant groups (control and hydrogen groups). However, compared with the control group, exposure to 3% hydrogen significantly improved lung graft static compliance and oxygenation and remarkably decreased the wet-to-dry weight ratio, inflammatory reactions, and lipid peroxidation. Furthermore, hydrogen improved the lung graft histological changes, decreased the lung injury score and apoptotic index and reduced NF-κB nuclear accumulation in the lung grafts.

CONCLUSION

Lung inhalation with 3% hydrogen during the warm ischemia phase attenuated lung graft IRI via NF-κB-dependent anti-inflammatory and antioxidative effects in rat donors after cardiac death.

摘要

背景

成功改善心脏死亡供体(DCD)的长期热缺血性肺损伤可以显著改善结局。氢气具有针对缺血再灌注损伤(IRI)的强大抗炎和抗氧化作用。本研究观察了在心脏死亡供体的热缺血期内吸入氢气对肺移植物的影响。

方法

心脏死亡后,大鼠供体肺(n=8)在原位进行 2 h 的热缺血期机械通气,通气条件为 40%氧气加 60%氮气(对照组)或 3%氢气加 40%氧气加 57%氮气(氢气组)。然后,在 2 h 的冷储存和 3 h 的受体再灌注后进行肺移植,然后对肺移植物进行评估。未进行移植的大鼠进行左侧开胸手术作为假手术组(n=8)。评估受体的静态顺应性和动脉血气分析结果。在再灌注 3 h 后评估湿重与干重比(W/D)、炎症、氧化应激、细胞凋亡和组织学变化。通过 Western blot 分析移植肺中核因子 kappa B(NF-κB)蛋白的表达。

结果

与假手术组相比,两组移植肺(对照组和氢气组)的肺功能、W/D、炎症反应、氧化应激和组织学变化均降低。然而,与对照组相比,暴露于 3%氢气可显著改善肺移植物的静态顺应性和氧合作用,并显著降低 W/D 比、炎症反应和脂质过氧化。此外,氢气改善了肺移植物的组织学变化,降低了肺损伤评分和细胞凋亡指数,并减少了 NF-κB 在肺移植物中的核积累。

结论

在心脏死亡供体的热缺血期内,肺内吸入 3%氢气通过 NF-κB 依赖性抗炎和抗氧化作用减轻了肺移植物的 IRI。

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