摘要
目的:探讨纤溶酶原激活物抑制物-1(PAI-1)在支气管哮喘(简称哮喘)小鼠气道炎症反应中的作用。方法:将野生型(WT)和PAI-1基因敲除(PAI-1^(-/-))小鼠随机分为野生型对照组(NS/WT组)、基因敲除对照组(NS/PAI-1^(-/-)组)、野生型哮喘组(OVA/WT组)和基因敲除哮喘组(OVA/PAI-1^(-/-)组)。通过腹腔注射和雾化吸入卵白蛋白(OVA)建立哮喘模型。肺泡灌洗液(BALF)行细胞分类计数;肺组织行HE染色和免疫组化。Luminex法检测血浆中IL-4、IL-13、IL-10、IL-2、INF-γ的含量。结果:PAI-1基因敲除使哮喘小鼠BALF中的中性粒细胞数量显著升高(P<0.01),对总炎症细胞数、嗜酸性粒细胞数、淋巴细胞数的改变不明显;PAI-1基因敲除使哮喘小鼠肺组织炎症细胞浸润加重、CD68表达量增加、血浆IL-10和INF-γ水平显著降低(P<0.05或P<0.01),IL-4、IL-13、IL-2水平无显著变化。结论:PAI-1基因缺失促进哮喘小鼠肺部炎症细胞募集,降低血浆IL-10和INF-γ水平,加重炎症反应。
Objective:To investigate the effects of plasminogen activator inhibitor 1(PAI-1)on airway inflammation in mouse with bronchial asthma.Methods:Wild type(WT)and PAI-1 knockout(PAI-1^(-/-))mice were randomly and equally divided into WT control group(NS/WT),PAI-1^(-/-)control group(NS/PAI-1^(-/-)),WT asthma group(OVA/WT)and PAI-1^(-/-)asthma group(OVA/PAI-1^(-/-)).The asthma model was established by intraperitoneal injection and aerosol inhalation of ovalbumin(OVA).The cell numbers in BALF were counted.Hematoxylin and eosin(HE)staining and immunohistochemistry were performed in lung sections.Magnetic Luminex were used to quantified the levels of IL-4,IL-13,IL-10,IL-2 and INF-γin plasma.Results:PAI-1 knockout could increase the neutrophils in the BALF of asthmatics(P<0.01),but could not influence the counts of total inflammatory cells,eosinophils and lymphocytes significantly.The infiltration of inflammatory cells and the expression of CD68 were increased in the lung of asthmatics after PAI-1 knockout.PAI-1 knockout could decrease the levels of IL-10 and INF-γsignificantly(P<0.05 or P<0.01),but could not influence the levels of IL-4,IL-13 and IL-2 obviously.Conclusion:PAI-1 knockout increases the airway inflammation in asthmatics by promoting inflammatory cells aggregation in the lung and decreasing the levels of IL-10 and INF-γin plasma.
作者
周霞
杜春玲
ZHOU Xia;DU Chunling(Department of Pulmonary and Critical Care Medicine,Qingpu Branch of Zhongshan Hospital Affiliated To Fudan University,Shanghai City 201700)
出处
《医学理论与实践》
2023年第11期1801-1804,共4页
The Journal of Medical Theory and Practice
基金
复旦大学附属中山医院青浦分院探索项目(QYT2021-01)
上海市医学重点专科建设(ZK2019B06)。