Prevention and treatment for reperfusion injuny in thoracic surgery

胸外科再灌注损伤的防治

• 批准号: 11470270
• 负责人: WADA Hiromi
• 金额: $ 7.42万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11470270/
• 关键词: ischemia-reperfusion injury; Selection blocken; reactive oxygen species; DNA damage; 8-OHdG(8-hydroxy-2'-deoxyguanosine); oxidative stress; MPO; 肺移植; ADF; Thioredoxin; Thioredoxine

Importance of reactive oxygen species released through interaction of leukocyte-endothelial cell in ischemia-reperfusion injury of the lung is not yet fully understood. A novel selectin blocker OJ-R9188, which inhibits the interaction may alleviate oxidative stress and pulmonary dysfunction after warm ischemia reperfusion. Rat lungs were reperfused at 37℃ for 60 min with an ex vivo model, and were divided into three groups (n=10). In Fresh group, lungs were reperfused immediately after harvest. In OJ-R (-) and OJ-R (+) groups, lungs were reperfused after warm ischemia at 37℃ for 90 min. In OJ-R (+) group, rats received 100 μg/body of OJ-R9188 intravenously 10 min before the harvest. Electron spin resonance method was used to assess the direct scavenging activity of OJ-R9188. Both shunt fractions and wet/dry weight ratios of the lung tissue after reperfusion in OJ-R (+) group were significantly lower than those in OJ-R (-) group. Oxidative DNA damage in the alveolar wall of OJ-R (+) group, assessed by immunohistochemical quantitation of 8-hydroxy-2'deoxyguanosine, was significantly lower than that of OJ-R (-) group. Immunostaining of 3-nitro-L-tyrosine, which represents nitric oxide-mediated oxidative damage, was also more intense in OJ-R (-) group than in OJ-R (+) group. Direct scavenging activity of OJ-R9188 was not observed, and the number of leukocytes infiltrated to the lung tissue as seen by myeloperoxidase activity was not different between OJ-R (-) and OJ-R (+) groups. A novel selectin blocker OJ-R9188 improves pulmonary function after warm ischemia-reperfusion and alleviates reperfusion-induced oxidative alveolar damage.

通过白细胞-内皮细胞相互作用释放的活性氧在肺缺血再灌注损伤中的重要性尚不完全清楚。新型选择素阻滞剂OJ-R9188可抑制这种相互作用，从而减轻热缺血再灌注后的氧化应激和肺功能障碍。大鼠肺以37℃复灌60min，分为3组(n=10)。新鲜组于收获后即刻行肺再灌流。OJ-R(-)组和OJ-R(+)组在37℃热缺血90min后复灌。OJ-R(+)组于收获前10min静脉注射OJ-R9188 100μg/只。用电子自旋共振方法评价了OJ-R9188的直接清除活性。OJ-R(+)组再灌流后肺组织的分流分数和湿/干重比均显著低于OJ-R(-)组。8-羟基-2‘-脱氧鸟苷免疫组织化学定量检测显示，OJ-R(+)组肺泡壁DNA氧化损伤明显低于OJ-R(-)组。代表一氧化氮介导的氧化损伤的3-硝基-L酪氨酸的免疫染色在OJ-R(-)组也比OJ-R(+)组更强。未观察到OJ-R9188的直接清除活性，髓过氧化物酶活性显示OJ-R(-)组和OJ-R(+)组肺组织中的白细胞数无差异。新型选择素阻滞剂OJ-R9188可改善热缺血再灌流后的肺功能，减轻再灌流所致的肺泡氧化损伤。

项目成果

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Kawashima M 等人：“硝酸甘油在缺血再灌注引起的肺损伤中的细胞保护作用”美国呼吸与重症监护医学杂志。

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Fukuse T: "Influence of deflated and anaerobic conditions during cold storage on rat lungs."American Journal of Respiratory and Critical Care Medicine. 160. 621-627 (1999)

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磯和理貴: "保存肺の酸化ストレス"THE LUNG perspectives. 9(1). 77-82 (2001)

Riki Iso：“储存肺中的氧化应激”THE LUNG 观点 77-82 (2001)。

Kawashima M.: "Cytoprotective effects of nitroglycerin in ischemia reperfusion induced lung injury"American Journal of Respiratory and Critical Care Medicine. (in press).

Kawashima M.：“硝酸甘油在缺血再灌注引起的肺损伤中的细胞保护作用”美国呼吸与重症监护医学杂志。