Prevention and treatment for reperfusion injuny in thoracic surgery

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。一种新型的选择素阻断剂OJ-R9188，其抑制相互作用可能减轻热缺血再灌注后的氧化应激和肺功能障碍。取大鼠肺在37℃下再灌注60 min，建立离体模型，并分为3组（n=10）。Fresh组在收获后立即进行肺再灌注。OJ-R（-）组和OJ-R（+）组在37℃热缺血90min后进行肺再灌注。OJ-R（+）组大鼠于采收前10 min静脉注射OJ-R9188 100 μg/体。采用电子自旋共振法评价了OJ-R9188的直接清除活性。OJ-R（+）组再灌注后肺组织分流分数和干湿重比均显著低于OJ-R（-）组。8-羟基-2’脱氧鸟苷免疫组化定量评价OJ-R（+）组肺泡壁DNA氧化损伤明显低于OJ-R（-）组。OJ-R（-）组3-硝基- l -酪氨酸的免疫染色也比OJ-R（+）组更强烈，代表一氧化氮介导的氧化损伤。没有观察到OJ-R9188的直接清除活性，并且通过髓过氧化物酶活性观察到浸润到肺组织的白细胞数量在OJ-R（-）组和OJ-R（+）组之间没有差异。新型选择素阻滞剂OJ-R9188可改善热缺血-再灌注后肺功能，减轻再灌注诱导的肺泡氧化损伤。

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.