Pretreatment with recombined human erythropoietin attenuates ischemia-reperfusion-induced lung injury in rats.

OBJECTIVE

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.

METHODS

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.

RESULTS

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).

CONCLUSIONS

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.