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Evaluation of a mouse model of chronic obstructive pulmonary disease induced by intraperitoneal injections of cigarette smoke extract

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Author:
No author available
Journal Title:
Chinese Journal of Tuberculosis and Respiratory Diseases
Issue:
4
DOI:
10.3760/cma.j.issn.1001-0939.2015.04.010
Key Word:
肺疾病,慢性阻塞性;肺气肿;模型,动物;烟草烟雾提取物;Obstructive pulmonary disease,chronic;Emphysema;Model,animal;Cigarette smoke extract

Abstract´╝Ü Objective To evaluate a mouse model of chronic obstructive pulmonary disease (COPD) induced by intraperitoneal injections of cigarette smoke extract (CSE),and to study the potential mechanisms.Methods Mice were injected intraperitoneally with CSE at different time points to establish a mouse model of COPD.Mouse lung mechanics parameters were measured,and the total numbers and differentials of cells in bronchoalveolar lavage fluid (BALF) were counted.Pathological changes of lung tissue were observed and mean linear intercept (MLI) and alveolar destructive index (DI) were measured.The expressions of matrix metalloproteinases-12 (MMP12),neutrophil elastase (NE),tissue inhibitor of metalloproteinase-1 (TIMP1),pro-inflammatory cytokines (TNF-α,IL-1β,IL-6),Th1 cytokines (IFN-γ),Th2 cytokines (IL-5,IL-13) and the neutrophil chemokine KC were determined in the lungs of all mice.Results Significant increase of total lung capacity (TLC) [(0.73 ± 0.02),(0.83 ± 0.04),(O.97 ±0.02) ml] was found in the CSE group as compared with the PBS control group [(0.65 ± 0.01),(0.67 ±0.02),(0.71 ±0.04)ml,t=4.109,3.666,5.994,P<0.01] at day 21,41,61.Lung compliance was higher in the CSE group [(0.041 ±0.002) ml/cmH2O (1 cmH2O =0.098 kPa),(0.039 ±0.001) ml/cmH2O] than the PBS control group [(0.030 ± 0.001) ml/cmH2O,(0.032 ± 0.003) ml/cmH2O,t =4.788,2.508,P <0.05] at day 41,61,but airway resistance in the lungs (R) was lower in the CSE group [(0.959 ±0.016) cmH2O · s · ml-1,(0.976 ±0.020) cmH2O · s · ml-1] than the PBS control group [(1.043±0.022) cmH2O · s · ml-1,(1.085 ±0.043) cmH2O · s · ml-1] (t=2.928,2.321,P<0.05).The total numbers of BALF cells in the CSE group [(23.83 ±2.63) × 104,(20.67 ± 1.69) × 104,(18.67 ± 1.56) × 104] were increased compared with the PBS control group [(7.33 ± 0.61) × 104,(7.67±0.76) × 104,(6.67 ±0.88) × 104,t =6.119,7.027,6.685,P <0.01] at day 21,41,61,predominantly with neutrophils and macrophages.Typical COPD pathological changes of lung tissue were evident,including Inflammatory cell infiltration in the lung parenchyma and increased mean linear intercept (MLI) in the CSE group [(48.0 ± 1.4),(56.1 ± 2.4),(59.3 ± 3.3) μm] as compared with the PBS control group [(40.5 ± 1.2),(43.7 ± 1.2),(43.5 ± 1.2)μm,t =4.015,4.695,4.612,P < 0.01] aswell as increased alveolar destructive index (DI) in the CSE group [(15.2 ± 1.3) %,(22.4 ± 1.3) %,(23.8 ± 1.0) %] as compared with the PBS control group [(11.1 ± 0.9) %,(10.8 ± 1.0) %,(12.4 ±0.7)%,t =2.532,7.225,8.471,P < 0.05] at the 3 time points.The expressions of MMP12 and NE increased significantly in the CSE-treated mice.Pro-inflammatory cytokines (TNF-α,IL-1β,L-6),Th1 cytokine IFN-γand KC all increased significantly in the CSE-treated mice as compared with the PBS-control mice.Conclusions A mouse model of COPD was successfully established by repeated intraperitoneal injections of CSE in a shorter period of time.Local inflammation and proteinase/anti-proteinase imbalance as a result of CSE-induced immunological responses may be the underlying mechanisms.

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