Wu Haiwei, Ren Binhui, Zhu Jiaquan, Dong Guohua, Xu Biao, Wang Changtian, Zheng Xiaogang, Jing Hua
Department of Cardiothoracic Surgery, Jingling Hospital, Clinical Medicine School of Nanjing University, 305 Zhongshan East Road, Nanjing 210002, China.
Eur J Cardiothorac Surg. 2006 Jun;29(6):902-7. doi: 10.1016/j.ejcts.2006.02.036. Epub 2006 May 3.
Based on the findings that erythropoietin (EPO) has been proved to be a multiple functional cytokine to attenuate ischemia-reperfusion (I/R) injury in various organs such as brain, heart, and kidney in animals, this experiment was designed to evaluate the effect of pretreatment with recombined human erythropoietin (rhEPO) on I/R-induced lung injury.
Left lungs of rats underwent 90 min of ischemia and then were reperfused for up to 2 h. Animals were randomly divided into three experimental groups as sham group, I/R group, and rhEPO + I/R group (a single dose of rhEPO was injected intraperitoneally 3000 U/kg 24 h prior to operation). Lung injury was evaluated according to semi-quantitative analysis of microscopic changes, tissue polymorphonuclear neutrophils (PMNs) accumulation (myeloperoxidase (MPO) activity), and pulmonary microvascular permeability (Evan's blue dying method). Peripheral arterial and venous blood samples were obtained for blood-gas analysis after 5 min occlusion of right lung hilus at the end of reperfusion. The serum concentration of tumor necrosis factor (TNF)-alpha was also measured by the method of enzyme-linked immunosorbent assay.
Histological injury scoring revealed significantly lessened lung alveolus edema and neutrophils infiltration in the rhEPO pretreated group compared with I/R group (p < 0.05). The rhEPO pretreated animals exhibited markedly decreased lung microvascular permeability (p < 0.05) and myeloperoxidase activity (p < 0.05). Blood-gas analysis demonstrated that the pretreated animals had significantly ameliorated pulmonary oxygenation function (p < 0.05). The serum concentration of tumor necrosis factor-alpha in rhEPO pretreated group was markedly decreased compared with that of I/R group (p < 0.05).
Pretreatment with rhEPO appears to attenuate I/R-induced lung injury. This function is partly related with the capacity that rhEPO inhibits the accumulation of polymorphonuclear neutrophils in lung tissue and decreases the systematic expression of tumor necrosis factor-alpha.
鉴于已证实促红细胞生成素（EPO）是一种多功能细胞因子，可减轻动物脑、心脏和肾脏等多种器官的缺血再灌注（I/R）损伤，本实验旨在评估重组人促红细胞生成素（rhEPO）预处理对I/R诱导的肺损伤的影响。
大鼠左肺进行90分钟缺血，然后再灌注长达2小时。动物被随机分为三个实验组，即假手术组、I/R组和rhEPO + I/R组（在手术前24小时腹腔注射单剂量rhEPO 3000 U/kg）。根据显微镜下变化的半定量分析、组织多形核中性粒细胞（PMN）积聚（髓过氧化物酶（MPO）活性）和肺微血管通透性（伊文思蓝染色法）评估肺损伤。在再灌注结束时，右肺门阻断5分钟后采集外周动脉和静脉血样本进行血气分析。还采用酶联免疫吸附测定法测量血清肿瘤坏死因子（TNF）-α浓度。
组织学损伤评分显示，与I/R组相比，rhEPO预处理组的肺泡水肿和中性粒细胞浸润明显减轻（p < 0.05）。rhEPO预处理的动物肺微血管通透性（p < 0.05）和髓过氧化物酶活性（p < 0.05）显著降低。血气分析表明，预处理的动物肺氧合功能明显改善（p < 0.05）。rhEPO预处理组的血清肿瘤坏死因子-α浓度与I/R组相比明显降低（p < 0.05）。
rhEPO预处理似乎可减轻I/R诱导的肺损伤。该功能部分与rhEPO抑制肺组织中多形核中性粒细胞积聚和降低肿瘤坏死因子-α的全身表达能力有关。
