中国病理生理杂志2024，Vol.40Issue(7)：1222-1229,8.DOI:10.3969/j.issn.1000-4718.2024.07.009
香烟烟雾联合Poly I:C诱导COPD模型小鼠气道上皮屏障损伤的机制
Mechanism of airway epithelial barrier injury in a mouse model of COPD induced by cigarette smoke exposure combined with Poly I:C
摘要
Abstract
AIM:To establish a mouse model of chronic obstructive pulmonary disease(COPD)induced by cigarette smoke(CS)exposure combined with polyinosinic-polycytidylic acid(Poly I:C)nasal drip,and to investigate the mechanism of airway epithelial barrier injury in COPD.METHODS:(1)Ninety-six male BALB/c mice were randomly divided into control group,CS group,Poly I:C group,and CS+Poly I:C group(n=24).The model was established from week 1 to week 8,with pulmonary function tested every 4 weeks.Six mice from each group were sacrificed at the end of weeks 4,8,16,and 24.Changes in minute volume(MV),enhanced pause(Penh),mean linear intercept(MLI)and bronchial wall thickness(BWT)were observed.The protein levels of interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),zonula occludens-1(ZO-1)and E-cadherin(E-Cad)in the lung were detected.(2)Human bronchial epithe-lial BEAS-2B cells were stimulated with CS extract(CSE)combined with Poly I:C for 24 h,and then the protein levels of occludin(Occ),ZO-1,and phosphorylated epidermal growth factor receptor(EGFR),P38 and extracellular signal-regu-lated kinase(ERK)1/2 were analyzed.RESULTS:(1)Compared with control group,at the 8th week,the mice in CS and CS+Poly I:C groups showed typical pathological changes in lung tissues,including significant inflammatory cell infil-tration,alveolar cavity expansion,alveolar wall rupture and fusion,and airway wall thickening.The Penh,BWT,MLI,and lung IL-1β and TNF-α levels were significantly increased(P<0.05 or P<0.01),while MV and lung ZO-1 and E-Cad levels were remarkably decreased(P<0.05 or P<0.01).By the 24th week,these pathological changes remained relative-ly stable in CS+Poly I:C group.(2)Compared with control group,CSE and its combination with Poly I:C dramatically in-duced a reduction in ZO-1 and Occ protein expression in BEAS-2B cells(P<0.05 or P<0.01),and increased the levels of phosphorylated EGFR,P38 and ERK1/2(P<0.01).The effects in CSE combined with Poly I:C group were considerably superior to those in CSE or Poly I:C group alone.CONCLUSION:Poly I:C can enhance the pathological changes and airway epithelial barrier damage induced by CS in a mouse model of COPD,which may be related to the activation of EGFR/ERK/P38 signaling pathway.关键词
慢性阻塞性肺疾病/香烟烟雾/聚肌胞苷酸/气道上皮屏障Key words
Chronic obstructive pulmonary disease/cigarette smoke/polyinosinic-polycytidylic acid/airway epithelial barrier分类
医药卫生引用本文复制引用
谢媛,梅晓峰,陶柳颖,江宇航,李建生,赵鹏..香烟烟雾联合Poly I:C诱导COPD模型小鼠气道上皮屏障损伤的机制[J].中国病理生理杂志,2024,40(7):1222-1229,8.基金项目
国家自然科学基金资助项目(No.81973822) （No.81973822）
河南省科技研发计划联合基金项目(No.22301420070) （No.22301420070）
郑州市科技协同创新专项(No.2023XTCX045) （No.2023XTCX045）
