布地奈德对高氧致新生小鼠支气管肺发育不良及HMGB1/TLR4/NF-κB通路的影响  

Effects of budesonide on bronchopulmonary bysplasia and HMGB1/TLR4/NF-κB pathway in neonatal mice induced by hyperoxia

作　　者：何苗 He Miao(Department of Pharmacy,Hunan Children′s Hospital,Changsha 410007,China)

机构地区：[1]湖南省儿童医院药剂科

出　　处：《中国医师杂志》2019年第8期1199-1204,共6页Journal of Chinese Physician

摘　　要：目的探讨布地奈德(BUN)对高氧诱导支气管肺发育不良(BPD)新生小鼠高迁移率族蛋白1(HMGB1)、Toll样受体4(TLR4)、核因子κB(NF-κB)通路的影响。方法将80只小鼠随机分为对照组、模型组、BUN低、中、高剂量组,每组16只。对照组小鼠置于空气中,模型组、BUN低、中、高剂量组暴露于60%氧浓度环境中建BPD模型;建模24 h后,对照组、模型组每天雾化吸入生理盐水,BUN低、中、高剂量组分别雾化吸入1、2、4 ml BUN,每12小时一次,持续雾化直至小鼠处死。建模7、14 d,苏木素-伊红(HE)染色观察肺组织形态学变化;酶联免疫吸附试验法(ELISA)检测肺组织中白介素(IL)-1β、IL-6、肿瘤坏死因子-α(TNF-α)、丙二醛(MDA)水平,超氧化物歧化酶(SOD)活性;实时荧光定量PCR(qRT-PCR)、蛋白免疫印迹(WB)检测肺组织中HMGB1、TLR4、NF-κB水平。结果建模7、14 d模型组肺组织结构破坏严重,肺泡体积增大,形成肺大疱。BUN低、中、高剂量组随着BUN浓度的升高,肺组织变形逐渐好转,肺泡结构逐渐完整。与对照组相比,模型组建模7、14d肺组织中放射状肺泡数量下降;SOD活性降低;IL-1β、IL-6、TNF-α、MDA、HMGB1、TLR4、NF-κB mRNA和蛋白表达水平升高(P<0.05)。与模型组相比,BUN各剂量组建模7、14 d肺组织中放射状肺泡数量逐渐增多,SOD活性逐渐升高,IL-1β、IL-6、TNF-α、MDA表达水平逐渐降低,HMGB1、TLR4、NF-κB mRNA和蛋白表达水平逐渐降低,差异具有统计学意义(P<0.05)。结论 BUN可能通过调控HMGB1、TLR4、NF-κB通路抑制炎症因子水平和氧化应激反应,实现对BPD新生小鼠的保护作用。Objective To investigate the effects of budesonide (BUN) on high mobility group protein 1 (HMGB1)/toll-like receptor 4 (TLR4)/ nuclear factor κB (NF-κB) pathway in neonatal mice with hyperoxia-induced bronchopulmonary dysplasia (BPD).Methods 80 mice were randomly divided into control group,model group,low,medium and high dose BUN groups,with 16 mice in each group.Mice in the control group were exposed to air,and mice in model group and BUN low,medium and high dose groups were exposed to 60% oxygen to establish BPD model;After 24 hours of modeling,the control group and model group were inhaled with normal saline every day.The low,middle and high dose BUN groups inhaled (1,2,4 ml) BUN,respectively,12 h/times,and continued to inhale until the mice were executed.On the 7th and 14th days of the model establishment,hematoxylin-eosin (HE) staining was used to observe the morphological changes of lung tissue;the levels of interleukin (IL)-1β,IL-6,tumor necrosis factor-α(TNF-α),malondialdehyde (MDA) and superoxide dismutase (SOD) in lung tissues were detected by enzyme-linked immunosorbent assay (ELISA);the levels of HMGB1,TLR4 and NF-κB in lung tissue were detected by real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) and protein immunoblotting (WB).Results In the model group,the lung tissue structure was severely damaged and the alveolar volume was enlarged to form bullae on the 7th and 14th day.In low,middle and high dose groups,with the increase of BUN concentration,the lung tissue deformation gradually improved and the alveolar structure gradually became intact.Compared with the control group,the number of radial alveoli in the lung tissues of the model group decreased at 7th and 14th days;SOD activity decreased;the expression levels of IL-1β,IL-6,TNF-α,MDA,HMGB1,TLR4 and NF-κB mRNA and protein were increased (P<0.05).Compared with the model group,the number of radial alveoli and SOD activity in lung tissues of BUN groups increased gradually at 7th and 14th days ,while the levels of IL-1

关 键 词：布地奈德 高氧症 支气管肺发育不良 HMGB1蛋白质 Toll样受体4 NF-ΚB 小鼠 

分 类 号：R965[医药卫生—药理学]