PDF(Pubmed)
Abstract：
BACKGROUND: Mitochondrial dysfunction results in poor organ quality, negatively affecting the outcomes of lung transplantation. Whether hydrogen benefits mitochondrial function in cold-preserved donors remain unclear. The present study assessed the effect of hydrogen on mitochondrial dysfunction in donor lung injury during cold ischemia phase (CIP) and explored the underlying regulatory mechanism.
METHODS: Left donor lungs were inflated using 40% oxygen + 60% nitrogen (O group), or 3% hydrogen + 40% oxygen + 57% nitrogen (H group). Donor lungs were deflated in the control group and were harvested immediately after perfusion in the sham group (n = 10). Inflammation, oxidative stress, apoptosis, histological changes, mitochondrial energy metabolism, and mitochondrial structure and function were assessed. The expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were also analyzed.
RESULTS: Compared with the sham group, inflammatory response, oxidative stress, histopathological changes, and mitochondrial damage were severe in the other three groups. However, these injury indexes were remarkably decreased in O and H groups, with increased Nrf2 and HO-1 levels, elevated mitochondrial biosynthesis, inhibition of anaerobic glycolysis and restored mitochondrial structure and function compared with the control group. Moreover, inflation using hydrogen contributed to stronger protection against mitochondrial dysfunction and higher levels of Nrf2 and HO-1 when comparing with O group.
CONCLUSIONS: Lung inflation using hydrogen during CIP may improve donor lung quality by mitigating mitochondrial structural anomalies, enhancing mitochondrial function, and alleviating oxidative stress, inflammation, and apoptosis, which may be achieved through activation of the Nrf2/HO-1 pathway.
METHODS: Left donor lungs were inflated using 40% oxygen + 60% nitrogen (O group), or 3% hydrogen + 40% oxygen + 57% nitrogen (H group). Donor lungs were deflated in the control group and were harvested immediately after perfusion in the sham group (n = 10). Inflammation, oxidative stress, apoptosis, histological changes, mitochondrial energy metabolism, and mitochondrial structure and function were assessed. The expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were also analyzed.
RESULTS: Compared with the sham group, inflammatory response, oxidative stress, histopathological changes, and mitochondrial damage were severe in the other three groups. However, these injury indexes were remarkably decreased in O and H groups, with increased Nrf2 and HO-1 levels, elevated mitochondrial biosynthesis, inhibition of anaerobic glycolysis and restored mitochondrial structure and function compared with the control group. Moreover, inflation using hydrogen contributed to stronger protection against mitochondrial dysfunction and higher levels of Nrf2 and HO-1 when comparing with O group.
CONCLUSIONS: Lung inflation using hydrogen during CIP may improve donor lung quality by mitigating mitochondrial structural anomalies, enhancing mitochondrial function, and alleviating oxidative stress, inflammation, and apoptosis, which may be achieved through activation of the Nrf2/HO-1 pathway.
摘要：
背景：线粒体功能障碍导致器官质量差，负面影响肺移植的结果。氢是否有益于冷藏供体的线粒体功能尚不清楚。本研究评估了氢对冷缺血期（CIP）供体肺损伤中线粒体功能障碍的影响，并探讨了潜在的调节机制。
方法：使用40％氧气60％氮气（O组）对左供肺充气，或3%氢+40%氧+57%氮(H组)。在对照组中将供体肺放气，并在假手术组（n=10）灌注后立即收获。炎症，氧化应激，凋亡，组织学变化,线粒体能量代谢，并对线粒体结构和功能进行了评估。还分析了核因子红细胞2相关因子2（Nrf2）和血红素加氧酶-1（HO-1）的表达。
结果：与假手术组相比，炎症反应，氧化应激，组织病理学变化,其他三组的线粒体损伤严重。然而,这些损伤指数在O和H组显著下降，随着Nrf2和HO-1水平的增加，线粒体生物合成升高，与对照组相比，无氧糖酵解抑制，线粒体结构和功能恢复。此外，与O组相比，使用氢的膨胀有助于增强对线粒体功能障碍的保护作用，并提高Nrf2和HO-1的水平。
结论：在CIP期间使用氢气进行肺充气可能通过减轻线粒体结构异常来改善供体肺质量，增强线粒体功能，减轻氧化应激，炎症,和细胞凋亡，这可以通过激活Nrf2/HO-1途径来实现。
方法：使用40％氧气60％氮气（O组）对左供肺充气，或3%氢+40%氧+57%氮(H组)。在对照组中将供体肺放气，并在假手术组（n=10）灌注后立即收获。炎症，氧化应激，凋亡，组织学变化,线粒体能量代谢，并对线粒体结构和功能进行了评估。还分析了核因子红细胞2相关因子2（Nrf2）和血红素加氧酶-1（HO-1）的表达。
结果：与假手术组相比，炎症反应，氧化应激，组织病理学变化,其他三组的线粒体损伤严重。然而,这些损伤指数在O和H组显著下降，随着Nrf2和HO-1水平的增加，线粒体生物合成升高，与对照组相比，无氧糖酵解抑制，线粒体结构和功能恢复。此外，与O组相比，使用氢的膨胀有助于增强对线粒体功能障碍的保护作用，并提高Nrf2和HO-1的水平。
结论：在CIP期间使用氢气进行肺充气可能通过减轻线粒体结构异常来改善供体肺质量，增强线粒体功能，减轻氧化应激，炎症,和细胞凋亡，这可以通过激活Nrf2/HO-1途径来实现。
