Page 17 - 南京医科大学自然版

第44卷第7期 南京医科大学学报（自然科学版）
2024年7月 Journal of Nanjing Medical University（Natural Sciences） ·901 ·

·基础研究·

阿奇霉素对高氧暴露新生大鼠肺损伤保护作用的研究

王燕琼，黄智峰，陈雪雨，韩东山，林冰纯，黄子璐，杨传忠 *
南方医科大学第一临床医学院，深圳市妇幼保健院新生儿科，广东 深圳 518000

［摘 要］ 目的：探讨阿奇霉素（azithromycin，AZM）对治疗新生大鼠支气管肺发育不良（bronchopulmonary dysplasia，BPD）的
有效性。方法：将新生大鼠随机分成空气⁃生理盐水（RA⁃Saline）组、空气⁃阿奇霉素（RA⁃AZM）组、氧气⁃生理盐水（O2⁃Saline）组、
氧气⁃阿奇霉素（O2⁃AZM）组，O2⁃Saline组和O2⁃AZM组大鼠组在出生12 h内暴露于浓度为95%~100%的高氧中以建立BPD新生
大鼠模型，RA⁃AZM组、O2⁃AZM组在生后第1~10天每天腹腔注射AZM（40 mg/kg），RA⁃Saline组和O2⁃Saline组给予等剂量的生
理盐水，观察大鼠的生存率；qPCR检测炎症因子和趋化因子的表达；测量肺泡平均线性截距（mean linear intercept，MLI）及次级
肺泡隔的生成、肺血管密度来评估AZM对BPD新生大鼠肺发育的影响，并通过免疫组化检测肺组织中性粒细胞及巨噬细胞来
评估AZM对炎症细胞的影响。结果：与O2⁃Saline组比较，O2⁃AZM组大鼠10 d存活率差异无统计学意义（P > 0.05）；qPCR结果
显示，与 O2⁃Saline 组比较，O2⁃AZM 组大鼠白介素⁃6（interleukin⁃6，IL⁃6）、单核细胞趋化蛋白⁃1（monocyte chemotactic protein⁃1，
MCP⁃1）、纤溶酶原激活物抑制剂⁃1（plasminogen activator inhibitor⁃1，PAI⁃1）表达显著下降（P < 0.05），中性粒细胞趋化因子⁃1
（cytokine induced neutrophil chemoattractant⁃1，CINC⁃1）表达差异无统计学意义（P > 0.05）；ELISA 结果表明，与 O2⁃Saline 组比
较，O2⁃AZM组大鼠IL⁃6水平显著下降（P < 0.05）；免疫组化结果显示，O2⁃AZM组大鼠肺组织巨噬细胞及中性粒细胞聚集显著
减少，肺血管密度及次级肺泡隔计数增加，差异均有统计学意义；HE 病理分析结果显示，与O2⁃Saline 组比较，O2⁃AZM 组大鼠
MLI显著缩短，差异有统计学意义（P < 0.05）。结论：AZM可降低高氧暴露新生大鼠肺组织炎症因子和趋化因子的释放，抑制炎
症细胞的趋化或募集，改善高氧暴露新生大鼠BPD样肺损伤。
［关键词］ 阿奇霉素；支气管肺发育不良；高氧暴露；炎症；肺发育
［中图分类号］ R722.6 ［文献标志码］ A ［文章编号］ 1007⁃4368（2024）07⁃901⁃08
doi：10.7655/NYDXBNSN240102

Investigation of the protective effect of azithromycin on pulmonary injury in neonatal rats
exposed to hyperoxia

WANG Yanqiong，HUANG Zhifeng，CHEN Xueyu，HAN Dongshan，LIN Bingchun，HUANG Zilu，YANG Chuanzhong *
Department of Neonatal，Shenzhen Maternal and Child Health Care Hospital，the First School of Clininical Medicine，
Southern Medical Unversity，Shenzhen 518000，China

［Abstract］ Objective：To investigate the effectiveness of azithromycin（AZM）on bronchopulmonary dysplasia（BPD）in neonatal
rats. Methods：Neonatal rats were randomly assigned to four groups：room air⁃saline（RA⁃Saline）group，room air⁃azithromycin
（RA⁃AZM）group，oxygen⁃saline（O2⁃Saline）group，and oxygen⁃azithromycin（O2⁃AZM）group. The O2⁃Saline group and O2⁃AZM
group were exposed to 95% to 100% oxygen within 12 hours of birth to establish a BPD rat model. The RA⁃AZM and O 2⁃AZM groups
received daily intraperitoneal injections of AZM at a dosage of 40 mg/kg from postnatal day 1 to day 10，while the RA⁃Saline and
O2⁃Saline groups were administered an equal volume of saline. The survival rate of the rats was carefully observed. qPCR analysis was
conducted to detect the expression of inflammatory factors and chemokines. Additionally，the alveolar mean linear intercept（MLI），the
formation of secondary alveolar septa，and pulmonary vascular density were measured to assess the impact of AZM on lung
development in BPD neonatal rats. Immunohistochemical detection of neutrophils and macrophages in lung tissue was also performed
to evaluate the anti⁃inflammatory effect of AZM on inflammatory cells. Results：Compared to the O 2⁃Saline group，the 10⁃day survival
rate of rats in the O 2 ⁃ AZM group did not exhibit a statistically significant difference（P > 0.05）. qPCR analysis revealed that the

［基金项目］ 深圳市“医疗卫生三名工程”（SZSM 202211001）；广东省高水平临床重点专科（SZGSP009）
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通信作者（Corresponding author），E⁃mail：yangczgd@163.com