香烟尘雾颗粒经鼻腔滴入建立小鼠COPD肺功能损伤模型

Cigarette dust particles induced lung function injury of chronic obstructive pulmonary disease in mice

目的:应用香烟尘雾颗粒(DSP)滴鼻的方法构建小鼠慢性阻塞性肺病(COPD)肺功能损伤模型,并评价该方法复制COPD模型的效果。方法:将BALB/c小鼠随机分为正常对照组(control)组、LPS 100 mg/L组、DSP 0.75 mL/L组、DSP 1.5 mL/L组和DSP 3 mL/L组,滴鼻造模,连续30 d。FlexiVent肺功能检测仪检测各组小鼠气道阻力(Rrs)、气道弹性阻力(Ers)、呼吸系统动态顺应性(Crs)、准静态弹性(Est)、准静态顺应性(Cst)、主气道阻力(P-3/8Rn)、组织衰减(P-3/8G)和组织弹性(P-3/8H);Myograph法检测各组小鼠主支气管环对乙酰甲胆碱(Mach)诱发的气道阻力增加的影响;收集各组小鼠气管、肺组织,进行HE、Masson和间苯二酚品红染色。结果:DSP连续滴鼻30 d可引起小鼠Rrs、Ers、Est、P-3/8Rn增加(P<0.01),Crs、Cst、P-3/8G、P-3/8H降低(P<0.01);DSP可使Mach诱发的小鼠气管收缩量效曲线左移,增加气道对Mach的敏感性,且能显著增加Mach的最大收缩气道的效应(P<0.01);DSP可引起小鼠气道上皮下显著纤维化,胶原蛋白在气道基底膜下网状板沉积,网状板增厚,肺部支气管管腔严重变形,肺部可见大量炎症细胞浸润,肺泡壁肌纤维和胶原纤维显著增加。结论:香烟尘雾颗粒滴鼻30 d的方法能够较好地建立同人类COPD疾病特点一致的小鼠模型。

AIM:To investigate the pathogenesis of chronic obstructive disease(COPD)in mice by using nasal drip of cigarette dust particles(DSP)induced pulmonary function damage model.METHODS:BALB/c mice were randomly divided into control group,LPS 100 mg/L group,DSP 0.75 mL/L group,DSP 1.5 mL/L group and DSP 3 mL/L group for 30 days.The method of nasal drip was used for 30 days to establish the COPD model.Rrs,Ers,Crs,Est,Cst,P-3/8Rn,P-3/8G and P-3/8H were measured for evaluating lung function of the mice in each group by the method of FlexiVent.The effect on the increase of airway resistance induced by methacholine(Mach)was determined using main bronchial rings by Myograph method.The HE,Masson and Resorcinol fuchsin staining of mouse tracheas and lung tissues were conducted.RESULTS:Continuous nasal drip with DSP for 30 days increased Rrs,Ers,Est,P-3/8Rn and decreased Crs,Cst,P-3/8G and P-3/8H in the mice.DSP significantly shifted the dose-effect curve of tracheal contraction induced by Mach to the left,increased the sensitivity of the airway to Mach,and significantly increased the maximal contractile airway effect of Mach.Exposure to DSP caused fibrosis of airway subepithelial,deposition of collagen in the airway basement membrane under the reticular plate,induced reticular plate thickening,pulmonary bronchial lumen serious deformation,and the inflammatory cell infiltration in the lung of mice.Significantly increased alveolar wall muscle fibers and collagen fibers were also observed.CONCLUSION:The lung function and pathomorphological changes of COPD mice induced by 30 days nasal drip of cigarette dust particles were similar to those of human COPD.