ABSTRACT
Objective To investigate anti-inflammatory effect of recombinant human erythropoietin(rhEPO) on bronchopulmonary dysplasia in newborn rats exposed to hyperoxia.Methods Ninety-six Wistar newborn rats were randomly divided into 4 groups after birth:room air-exposed control group,room air-exposed rhEPO treated group,hyperoxia-exposed group,and the hyperoxia-exposed rhEPO treated group.The last two groups were exposed to oxygen,FiO2 =850 mL/L,room air-exposed rhEPO treated and hyperoxia-exposed rhEPO treated group received rhEPO 2 400 IU/kg subcutaneously at birth,30 minutes' before oxygen exposure and 2 d after birth.The isodose of 9 g/L saline was given in the same way in room air-exposed controls and hyperoxia-exposed pups.Rats from each group were sacrificed on day 3,7 and 10.Lung histology was observed under microscope,and mRNA expression of monocyte chemoattractant protein-1 (MCP-1) and cytokine-induced neutrophil hemoattractant-1 (CINC-1) were determined with reverse transcriotion-polymerase chain reaction(RT-PCR).Results Under microscope,in the hyperoxia-exposed group,inflammatory cell influx was detected in the lungs on the 3rd day and there was marked neutrophlic infiltrate on the 7th day.Alveolar enlargement and fibrosis were evident on the 10th day.At the same time,the histopathological changes were improved greatly in the lungs of hyperoxia-exposed rhEPO treated pups compared with the hyperoxia-exposed pups.MCP-1 and CINC-1 mRNA expression increased in hyperoxia-exposed pups,compared with room air-exposed controls especially on the 7th day [(0.94 ± 0.45) vs (0.21 ± 0.03),P ＜ 0.001 ; (1.26 ± 0.29) vs (0.26 ± 0.06),P ＜ 0.001].MCP-1 and CINC-1 mRNA expression were greatly depressed in the hyperoxia-exposed rhEPO treated pups compared with the hyperoxia-exposed pups especially on the 7th day.[(0.65 ± 0.07) vs (0.94 ± 0.45),P＜0.05;(0.83±0.07) vs (1.26±0.29),P＜0.05].Conclusions The therapy of rhEPO (2 400 IU/kg) therapy can reduce lung inflammatory cell infiltration and alveolar fibrin deposition in newborn rats with hyperoxic lung injury,and it can restrain MCP-1 and CINC-1 mRNA expression.The anti-inflammatory mechanism of rhEPO is related to inhibition of MCP-l and CINC-1 mRNA expression.