摘要
目的:建立小鼠慢性阻塞性肺疾病(COPD)模型,探讨噻托溴铵(TIO)是否能够通过调控核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)炎症小体活性发挥肺保护作用。方法:全身暴露香烟烟雾法构建COPD小鼠模型,部分采用TIO进行干预,分析小鼠的一般情况、肺功能指标、病理改变和肺部炎症细胞数量的变化。ELISA法检测小鼠支气管肺泡灌洗液(BALF)上清中白细胞介素1β(IL-1β)和IL-18的水平;Western blot法检测小鼠肺组织NLRP3及caspase-1蛋白的表达。结果:与对照组比较,COPD组小鼠体重、第100毫秒用力呼气容积(FEV100)、FEV100/用力肺活量(FVC)和动态肺顺应性(Cdyn)均明显下降(P<0.05),气道阻力(RI)明显升高(P<0.05),FVC水平无显著差异,肺组织平均肺泡间隔、BALF中炎症细胞、IL-1β和IL-18水平和肺组织中NLRP3及caspase-1蛋白表达均显著升高(P<0.05)。与COPD组比较,COPD+TIO组小鼠体重、FVC和Cdyn水平无显著差异,FEV100和FEV100/FVC明显升高(P<0.05),RI明显下降(P<0.05),肺组织平均肺泡间隔,BALF中炎症细胞、IL-1β和IL-18水平,以及肺组织中NLRP3和caspase-1蛋白表达均显著降低(P<0.05)。结论:TIO可以减轻COPD模型小鼠肺部炎症损伤,其机制可能与抑制NLRP3炎症小体的活化有关。
AIM:To investigate the potential lung-protective effects of tiotropium(TIO)in a mouse model of chronic obstructive pulmonary disease(COPD)and to explore whether its effects are mediated by inhibition of nucleotidebinding oligomerization domain-like receptor protein 3(NLRP3)inflammasome.METHODS:C57BL/6J mice were ex⁃posed to cigarette smoke for 6 months to establish a model of COPD.The mice were randomly divided into 3 groups:saline control group,cigarette smoke exposure group(COPD group),and cigarette smoke with TIO treatment(COPD+TIO)group,with 6 mice in each group.The mice were monitored for changes in general condition,lung function,pathological and inflammatory cells in the lungs.Enzyme-linked immunosorbent assay(ELISA)was used to measure the protein levels of interleukin(IL)-1βand IL-18 in the bronchoalveolar lavage fluid(BALF),and Western blot was used to detect the pro⁃tein levels of NLRP3 and caspase-1 in the lung tissues.RESULTS:Exposure to cigarette smoke resulted in significant de⁃creases in lung function parameters,including forced expiratory volume in 100 ms(FEV100),FEV100/forced vital capaci⁃ty(FVC)and dynamic lung compliance(Cdyn),as well as an increase in resistance index(RI)compared with control group(P<0.05).Additionally,the mice in COPD group exhibited decreased body weight and increased mean linear inter⁃cept in lung histopathology(P<0.05),but no significant difference in FVC compared with control group.Inflammatory cell infiltration,and the levels of IL-1βand IL-18 in BALF were dramatically increased in COPD group(P<0.05).Fur⁃thermore,NLRP3 and caspase-1 protein levels were increased in lung tissues of COPD group(P<0.05).Treatment with TIO attenuated the lung function decline,with increased FEV100 and FEV100/FVC,and decreased RI compared with COPD group(P<0.05).There were no significant differences in body weight,FVC and Cdyn between COPD group and COPD+TIO group.Treatment with TIO also reduced mean linear intercept in lung histopathology,inflammatory cell infil⁃tration,IL-1β
作者
徐慧
曹伟涛
白鸽
罗承娜
刘俊
赵子文
刘朝晖
赵祝香
XU Hui;CAO Weitao;BAI Ge;LUO Chengna;LIU Jun;ZHAO Ziwen;LIU Zhao-hui;ZHAO Zhuxiang(Department of Respiratory Medicine,Guangzhou First People's Hospital,The Second Affiliated Hospital,School of Medi-cine,South China University of Technology,Guangzhou 510180,China;State Key Laboratory of Respiratory Diseases,Guangzhou Institute of Respiratory Disease,The First Affiliated Hospital,Guangzhou Medical University,Guangzhou 510120,China.)
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2023年第5期838-845,共8页
Chinese Journal of Pathophysiology
基金
广东省自然科学基金资助项目(No.2019A1515011084)
国家自然科学基金资助项目(No.81970038)
广州市科技计划项目(No.202002030011)。
