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电子科技大学医学院附属妇女儿童医院/成都市妇女儿童中心医院新生儿重症医学科,成都 611731
副主任医师,硕士。研究方向:新生儿疾病。E-mail:vinasd@163.com
主任医师,硕士。研究方向:新生儿重症医学。E-mail:gaosqiang@126.com
纸质出版日期:2024-01-30,
收稿日期:2023-07-04,
修回日期:2023-08-03,
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杜维纳,高淑强,巨容等.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 Δ[J].中国药房,2024,35(02):155-159.
DU Weina,GAO Shuqiang,JU Rong,et al.Improvement effects of azithromycin on bronchopulmonary dysplasia in neonatal rats and its mechanism[J].ZHONGGUO YAOFANG,2024,35(02):155-159.
杜维纳,高淑强,巨容等.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 Δ[J].中国药房,2024,35(02):155-159. DOI: 10.6039/j.issn.1001-0408.2024.02.06.
DU Weina,GAO Shuqiang,JU Rong,et al.Improvement effects of azithromycin on bronchopulmonary dysplasia in neonatal rats and its mechanism[J].ZHONGGUO YAOFANG,2024,35(02):155-159. DOI: 10.6039/j.issn.1001-0408.2024.02.06.
目的
2
基于缺氧诱导因子1α(HIF-1α)/HIF-2α/血管内皮生长因子(VEGF)信号通路探讨阿奇霉素对新生大鼠支气管肺发育不良(BPD)的改善作用及机制。
方法
2
将60只新生SD大鼠随机分为阴性对照(NC)组、BPD组、阿奇霉素组、布地奈德组(阳性对照),每组15只。NC组大鼠正常呼吸空气,其余3组大鼠通过在高浓度氧中暴露14 d构建BPD大鼠模型。建模成功后,阿奇霉素组大鼠腹腔注射阿奇霉素200 mg/kg,布地奈德组大鼠雾化吸入布地奈德1.5 mg/kg,每日1次,连续14 d;BPD组和NC组大鼠不做任何处理。观察并检测各组大鼠肺组织病理学变化、放射状肺泡计数、肺泡平均截距,支气管肺泡灌洗液(BALF)中白细胞计数和肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)、IL-1β、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、丙二醛(MDA)水平,肺组织中VEGF、HIF-1α、HIF-2α mRNA相对表达量和蛋白表达量。
结果
2
与NC组比较,BPD组大鼠肺组织出现明显损伤;白细胞计数、肺泡平均截距和TNF-α、IL-6、IL-1β、MDA水平均显著上调;放射状肺泡计数,SOD、CAT水平,VEGF、HIF-1α、HIF-2α mRNA相对表达量和蛋白表达量均显著下调(
P
<0.05)。与BPD组比较,阿奇霉素组和布地奈德组大鼠上述指标均显著逆转(
P
<0.05)。
结论
2
阿奇霉素可明显改善新生大鼠BPD的不良症状,抑制炎症及氧化应激反应,其作用机制可能是通过激活HIF-1α/HIF-2α/VEGF信号通路来实现肺保护作用。
OBJECTIVE
2
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
2
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
2
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
2
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.
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
bronchopulmonary dysplasiaoxidative stressimmune regulationhypoxia-inducible factorvascular endothelial growth factor
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