Effects of recombinant human elafin on the expression of inflammatory factors and NF-κB p65 protein in neonatal mice with bronchopulmonary dysplasia induced by chronic hyperoxia

Abstract:

Objective：To investigate the effects of recombinant human elafin on the expression of inflammatory factors and nuclear factor-κB（NF-κB） p65 protein in neonatal mice with bronchopulmonary dysplasia（BPD） induced by chronic hyperoxia. Methods：A total of 30 C57BL/6J neonatal mice within postnatal 24 hours were equally and randomly divided into three groups：air group，hyper－oxia+Lactated-Ringer（L/R）-treated group（O2+L/R group，L/R solution as vehicle），and hyperoxia+elafin-treated group（O2+elafin group）. The O2+L/R group and the O2 +elafin group were exposed to 85% oxygen，while the air group was exposed to 21% oxygen（room air）. At 21 days of treatment，the baseline lung function was determined；HE staining was used to observe the morphological changes of the lung tissue；the mRNA expression of inflammatory factors was determined by real-time polymerase chain reaction and the expression of NF-κB p65 protein was determined by Western blot. Results：Compared with the air group，the O2+L/R group had a significantly lower body weight[（7.85±0.24） g vs. （5.33±0.63） g，P=0.000）] and delayed lung development；in addition，the O2+L/R group had significantly higher expression of tumor necrosis factor-α（TNF-α） mRNA（P=0.000），interleukin-1β（IL-1β） mRNA（P=0.000），and NF-κB p65 protein（P=0.001），but significantly lower expression of interleukin-4（IL-4） mRNA（P=0.000） and inter－leukin-13（IL-13） mRNA（P=0.000）. Compared with the O2+L/R group，the O2+elafin group had a significantly higher body weight（P=0.014） and relatively normal alveolar morphology；in addition，the O2+elafin group had significantly lower expression of TNF-α mRNA（P=0.011），IL-1β mRNA（P=0.000），and NF-κB p65 protein（P=0.001），but significantly higher expression of IL-4 mRNA（P=0.047） and IL-13 mRNA（P=0.000）. Conclusion：Elafin can effectively alleviate hyperoxia-induced lung injury in mice. The mechanism of action may be related to the inhibition of NF-κB activation and the release of inflammatory factors.