中国药房2024,Vol.35Issue(2):155-159,5.DOI:10.6039/j.issn.1001-0408.2024.02.06
阿奇霉素对新生大鼠支气管肺发育不良的改善作用及机制
Improvement effects of azithromycin on bronchopulmonary dysplasia in neonatal rats and its mechanism
摘要
Abstract
OBJECTIVE To investigate the improvement effects of azithromycin on bronchopulmonary dysplasia(BPD)in neonatal rats based on hypoxia-inducible factor-1α(HIF-1α)/HIF-2α/vascular endothelial growth factor(VEGF)pathway.METHODS Sixty newborn SD rats were randomly divided into negative control group(NC),BPD group,azithromycin group and budesonide group(positive control),with 15 rats in each group.Rats in NC group were given normal breathing air,while rats in other three groups were exposed to high-concentration oxygen for 14 days to establish BPD rat models.After successful modeling,rats in azithromycin group were intraperitoneally injected with azithromycin 200 mg/kg,and rats in budesonide group were atomized with budesonide 1.5 mg/kg once a day for 14 consecutive days,while rats in BPD group and NC group were not treated.Pathological changes of lung tissue,radial alveolar count and mean alveolar intercept of rats were observed in each group.The white blood cell count in bronchoalveolar lavage fluid(BALF)and the levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),IL-1β,superoxide dismutase(SOD),catalase(CAT)and malondialdehyde(MDA)were detected;mRNA and protein expressions of VEGF,HIF-1α,HIF-2α were also detected.RESULTS Compared with NC group,the lung tissue in BPD group was obviously damaged;the white blood cell count,average alveolar intercept and the levels of TNF-α,IL-6,IL-1β and MDA were significantly increased;the radial alveolar count,SOD and CAT levels,the relative expressions of VEGF,HIF-1α,HIF-2α mRNA and protein were significantly decreased(P<0.05).Compared with BPD group,the changes of the above indexes in azithromycin group and budesonide group were significantly reversed(P<0.05).CONCLUSIONS Azithromycin can obviously improve the symptoms of BPD in rats,reduce inflammation and oxidative stress,and exert lung protection,the mechanism of which may be realized by activating HIF-1α/HIF-2α/VEGF pathway.关键词
阿奇霉素/支气管肺发育不良/氧化应激/免疫调节/缺氧诱导因子/血管内皮生长因子Key words
azithromycin/bronchopulmonary dysplasia/oxidative stress/immune regulation/hypoxia-inducible factor/vascular endothelial growth factor分类
医药卫生引用本文复制引用
杜维纳,高淑强,巨容,习玉峰..阿奇霉素对新生大鼠支气管肺发育不良的改善作用及机制[J].中国药房,2024,35(2):155-159,5.基金项目
四川省科技计划项目(重点研发项目)(No.2022YFS0241) (重点研发项目)