miR-34a在高氧诱导新生大鼠支气管肺发育不良模型中的表达及调控机制  

Expression and regulatory mechanism of miR-34a in neonatal rat model of bron-chopulmonary dysplasia induced by hyperoxia

作　　者：霍梦月 梅花[1] 张钰恒 张艳波[1] 刘春丽[1] HUO Mengyue;MEI Hua;ZHANG Yuheng;ZHANG Yanbo;LIU Chunli(Department of Neonatology,Affiliated Hospital of Inner Mongolia Medical University,Hohhot 010050,China)

机构地区：[1]内蒙古医科大学附属医院新生儿科,呼和浩特010050

出　　处：《北京大学学报(医学版)》2025年第2期237-244,共8页Journal of Peking University:Health Sciences

基　　金：内蒙古自治区自然科学基金(2020MS08034);内蒙古医科大学附属医院重大科研项目(NYFY ZD008)。

摘　　要：目的:探讨miR-34a在高氧诱导新生大鼠支气管肺发育不良(bronchopulmonary dysplasia,BPD)模型肺组织中的表达及其可能的调控机制。方法:将80只新生SD大鼠于生后2 h内随机分配到高氧组(FiO 2=60%)及空气组(FiO 2=21%),每组40只,分别于生后第1、7、14、21天提取各组SD大鼠肺组织标本,HE染色后于光镜下观察肺组织病理变化,记录辐射状肺泡计数(radial alveolar counts,RAC),并测量平均肺泡直径(mean alveolar dia-meter,MAD)和肺泡间隔厚度(alveolar septal thickness,AST)以评价肺泡发育情况;应用实时荧光定量PCR技术检测不同时间点高氧组与空气组大鼠肺组织中miR-34a、血管生成素-1(angiopoietin-1,Ang-1)和酪氨酸激酶受体-2(tyrosine kinase receptor-2,Tie-2)的基因表达情况;应用酶联免疫吸附测定法(enzyme linked immunosorbent assays,ELISA)检测不同时间点两组大鼠肺组织中Ang-1及Tie-2蛋白的表达水平。结果:高氧组大鼠生后第7、14、21天体重较空气组降低,差异有统计学意义(P均<0.05)。高氧组大鼠肺组织随氧暴露时间的延长逐渐出现肺泡数量减少、体积增大、结构简单化、肺泡腔明显增大和肺泡间隔增厚等肺发育受阻表现;高氧组大鼠生后第7、14、21天RAC较空气组明显减少,差异有统计学意义(P均<0.05)。与空气组相比,高氧组大鼠生后第7、14、21天MAD和AST明显增加,差异有统计学意义(P均<0.05)。高氧组大鼠肺组织miR-34a在生后第7、14、21天的表达水平均明显高于空气组,差异有统计学意义(P均<0.05)。与同时间点空气组相比,高氧组大鼠肺组织中Ang-1和Tie-2 mRNA的表达水平和蛋白质的表达水平在生后第14、21天均低于空气组,差异有统计学意义(P均<0.05)。结论:将新生SD大鼠持续暴露于60%的高氧环境中可成功构建大鼠新型BPD模型,在新生大鼠新型BPD模型的肺组织中miR-34a表达上调,miR-34a可能通过调控Ang-1/Tie-2信号通路在BPD的发生发展�Objective:To investigate the expression and possible regulatory mechanism of miR-34a in the lung tissue of neonatal rat model of bronchopulmonary dysplasia(BPD)induced by hyperoxia.Methods:In the study,80 newborn SD rats were randomly divided into hyperoxia group(FiO 2=60%)and air group(FiO 2=21%)within 2 hours after birth,40 rats per group.Lung tissue samples of the SD rats in each group were extracted on the 1st,7th,14th and 21st days after birth,and the pathological changes of lung tissue were observed under light microscope after HE staining.The number of radial alveolar counts(RAC)and the mean alveolar diameter(MAD)and the thickness of alveolar septal thickness(AST)were measured to evaluate the development of alveoli.Real-time fluorescence quantitative PCR was used to detect the expression of miR-34a,angiopoietin-1(Ang-1)and tyrosine kinase receptor-2(Tie-2)in lung tissue of rats in hyperoxia group and air group at different time points.Enzyme-linked immunosorbent assay(ELISA)was used to detect the proteins expression of Ang-1 and Tie-2 in the lung tissues of the two groups at different time points.Results:The weight of rats in the hyperoxia group on the 7th,14th and 21st days after birth was significantly lower than that in the air group(P all<0.05).With the prolongation of oxygen exposure,the number of alveoli decreased,the volume increased,the structure simplified,the alveolar cavity enlarged obviously and the alveolar septum thickened in the hyperoxia group.On the 7th,14th and 21st days after birth,the RAC in the hyperoxia group was significantly lower than that in the air group(P all<0.05).Compared with the air group,MAD and AST increased significantly on the 7th,14th and 21st days after birth in the hyperoxia group,and the difference was statistically significant(P all<0.05).The expression level of miR-34a in lung tissue of hyperoxia group was significantly higher than that of air group on the 7th,14th and 21st days after birth,and the difference was statistically significant(P all<0.05).Compared with

关 键 词：支气管肺发育不良 微小RNA-34a 血管生成素-1 酪氨酸激酶受体-2 高氧 

分 类 号：R722.1[医药卫生—儿科] R332[医药卫生—临床医学]