Energy metabolism and reperfusion injury on cold ischemia of lungs.

肺冷缺血的能量代谢和再灌注损伤。

• 批准号: 10671250
• 负责人: FUKUSE Tatsuo
• 金额: $ 0.38万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671250/
• 关键词: Lung preservation; Mitochondria; Energy metabolism; Aerobic metabolism; Anaerobic metabolism; ATP; Reperfusion injury; Trehalose; 肺再灌流障害

We compared the preservative effects of a monosaccharide (glucose), disaccharides (trehalose, maltose, sucrose), and a trisaccharide (raffinose) to investigate whether or not the effects of saccharides on lung preservation depend on their molecular weight, energy-level maintenance and cytoprotective effects. The effects of saccharides may depend on their cytoprotective effect rather than on impairment activity or energy-level maintenance of the preserved lung. Trehalose proved to be superior to the other saccharides.Energy depletion closely correlates with ischemia-reperfusion (I-R) injury in solid organs, but there has been no conclusion about the lungs that contain air. We investigated the alveolar state during cold storage and its relation to energy metabolism and I-R injury in an ex-vivo rat lung model. The lung was deflated (DEF group) or inflated with either room air (RA group) or nitrogen (N2 group) for six hours at 4℃, and reperfused or bronchoalveolar lavage fluid (BALF) was collected (N=6, each). Furthermore, the static lung compliance, the intrapulmonary levels of high energy phosphates, lactate and pyruvate were measured. The pulmonary functions of the DEF and N2 groups were significantly worse than those of the RA group. In the N2 group, the intrapulmonary levels of energy charge and pyruvate/lactate ratio were significantly lower than those in the DEF and RA groups, while there were no significant differences between the DEF and RA groups. In the DEF group, total protein and lactate dehydrogenase in the BALF were significantly higher while the static lung compliance was significantly lower compared with the N2 and RA groups. We concluded that aerobic metabolism would be essential for attenuating I-R injury of the lung, and inflation of the alveoli would be necessary for avoiding mechanical damage during re-expansion.

我们比较了单糖(葡萄糖)、双糖(海藻糖、麦芽糖、蔗糖)和三糖(棉子糖)的保存效果，以探讨糖对肺保存的影响是否取决于它们的分子质量、能量水平维持和细胞保护作用。糖的作用可能取决于它们的细胞保护作用，而不是对保存的肺的损伤活动或能量水平的维持。海藻糖被证明优于其他糖。能量耗竭与实体器官的缺血再灌注(I-R)损伤密切相关，但关于含有空气的肺还没有结论。在大鼠离体肺模型上，研究了冷藏过程中肺泡的状态及其与能量代谢和I-R损伤的关系。在4℃时对肺进行放气(DEF组)或充入室内空气(RA组)或充气(N2组)6h，并收集再灌流或支气管肺泡灌洗液(n=6)。测定肺静态顺应性、肺内高能磷酸盐、乳酸和丙酮酸水平。DEF组和N2组肺功能明显差于RA组。N2组肺内能荷水平和丙酮酸/乳酸比值显著低于DEF组和RA组，而DEF组和RA组之间无显著差异。DEF组BALF中总蛋白和乳酸脱氢酶显著高于N2组和RA组，而静态肺顺应性显著低于N2组和RA组。我们的结论是有氧代谢是减轻肺I-R损伤的关键，肺泡充气是避免再扩张过程中机械损伤的必要条件。

项目成果

Fukuse T: "Energy metabolism and mitochondrial damage during pulmonary preservation"Transplant Proc. 31. 1937-1938 (1999)

Fukuse T：“肺保存过程中的能量代谢和线粒体损伤”移植过程。

Hirata T,Fukuse T,Wada H: "High-energy phosphates,mitochondria,and reperfusion injury in isolated rat lungs." Transplant Proc. 30. 3377-9 (1998)

Hirata T、Fukuse T、Wada H：“离体大鼠肺中的高能磷酸盐、线粒体和再灌注损伤。”

Ueda M,Hirata T,Fukuse T,et al.: "Mitochondrial Injuries in Rat Lungs Preserved for 17 Hours ; an Ultrastructural Study." European Surgical Research. (1998)

Ueda M、Hirata T、Fukuse T 等人：“保存 17 小时的大鼠肺中的线粒体损伤；一项超微结构研究”。

Fukuse T.: "Energy metabolism and reperfusion injury on warm and cold ischemia of inflated and deflated lungs"Transplant Proc. (in press).

Fukuse T.：“膨胀和收缩肺的热缺血和冷缺血的能量代谢和再灌注损伤”移植过程。

Fukuse T: "Energy metabolism and reperfusion injury on warm and cold ischemia of inflated and deflated lungs"Transplant Proc. (in press).

Fukuse T：“膨胀和收缩肺的热缺血和冷缺血的能量代谢和再灌注损伤”移植过程。