阿奇霉素对高氧暴露新生大鼠肺损伤保护作用的研究  

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

作　　者：王燕琼 黄智峰 陈雪雨 韩东山 林冰纯 黄子璐 杨传忠 WANG Yanqiong;HUANG Zhifeng;CHEN Xueyu;HAN Dongshan;LIN Bingchun;HUANG Ziu;YANG Chuanzhong(Department of Neonatal,Shenzhen Maternal and Child Health Care Hospital,the First School of Clininical Medicine,Southern Medical Unversity,Shenzhen 518000,China)

机构地区：[1]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

出　　处：《南京医科大学学报（自然科学版）》2024年第7期901-908,共8页Journal of Nanjing Medical University(Natural Sciences)

基　　金：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)。

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;q PCR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。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 O2-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 O2-Saline group,the 10-day survival rate of rats in the O2-AZM group did not exhibit a statistically significant difference(P>0.05).qPCR analysis revealed that the expressions of interleukin-6(IL-6),monocyte chemotactic protein-1(MCP-1),and plasminogen activator inhibitor-1(PAI-1)were significantly reduced in the O2-AZM group compared to the O2-Saline group(P<0.05),while the expression of cytokine induced neutrophil chemoattractant-1(CINC-1)showed no significant difference(P>0.05).ELISA analysis further confirmed a significant reduction in IL-6 levels in the O2-AZM group compared to the O2-Saline group(P<0.05).Immunohistochemical analysis revealed a marked reduction in the accumulation of macrophages and neutrophils in the lung tissues of the O2-AZM group,along with an increase in pulmonary vascular density and the count of secondary alveolar

关 键 词：阿奇霉素 支气管肺发育不良 高氧暴露 炎症 肺发育 

分 类 号：R722.6[医药卫生—儿科]