Effects of budesonide on bronchopulmonary bysplasia and HMGB1/TLR4/NF-κB pathway in neonatal mice induced by hyperoxia / 中国医师杂志

ABSTRACT

Objective To investigate the effects of budesonide (BUN) on high mobility group protein 1 (HMGB1)/toll-like receptor 4 (TLR4) / nuclear factor κB (NF-κB) pathway in neonatal mice with hyperoxia-induced bronchopulmonary dysplasia (BPD).Methods 80 mice were randomly divided into control group,model group,low,medium and high dose BUN groups,with 16 mice in each group.Mice in the control group were exposed to air,and mice in model group and BUN low,medium and high dose groups were exposed to 60％ oxygen to establish BPD model;After 24 hours of modeling,the control group and model group were inhaled with normal saline every day.The low,middle and high dose BUN groups inhaled (1,2,4 ml) BUN,respectively,12 h/times,and continued to inhale until the mice were executed.On the 7th and 14th days of the model establishment,hematoxylin-eosin (HE) staining was used to observe the morphological changes of lung tissue;the levels of interleukin (IL)-1β,IL-6,tumor necrosis factor-α (TNF-α),malondialdehyde (MDA) and superoxide dismutase (SOD) in lung tissues were detected by enzyme-linked immunosorbent assay (ELISA);the levels of HMGB1,TLR4 and NF-κB in lung tissue were detected by real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) and protein immunoblotting (WB).Results In the model group,the lung tissue structure was severely damaged and the alveolar volume was enlarged to form bullae on the 7th and 14th day.In low,middle and high dose groups,with the increase of BUN concentration,the lung tissue deformation gradually improved and the alveolar structure gradually became intact.Compared with the control group,the number of radial alveoli in the lung tissues of the model group decreased at 7th and 14th days;SOD activity decreased;the expression levels of IL-1β,IL-6,TNF-α,MDA,HMGB1,TLR4 and NF-κB mRNA and protein were increased (P ＜0.05).Compared with the model group,the number of radial alveoli and SOD activity in lung tissues of BUN groups increased gradually at 7th and 14th days,while the levels of IL-1β,IL-6,TNF-α,MDA,HMGB1,TLR4and NF-κB decreased gradually at different doses (P ＜ 0.05).Conclusions BUN may inhibit the levels of inflammatory factors and oxidative stress by regulating HMGB1/TLR4/NF-κB pathway to achieve the protective effect on BPD neonatal mice.