Development and characterization of a rat model of chronic obstructive pulmonary disease (COPD) induced by sidestream cigarette smoke

被引:85
作者
Zheng, Hongao [1 ]
Liu, Yuening [1 ]
Huang, Tian [1 ]
Fang, Zheman [1 ]
Li, Guishuang [1 ]
He, Shaoheng [1 ,2 ]
机构
[1] Shantou Univ, Allergy & Inflammat Res Inst, Key Inmunopathol Lab Guangdong Prov, Coll Med, Shantou, Guangdong, Peoples R China
[2] Nanjing Med Univ, Clin Res Ctr, Affiliated Hosp 1, Nanjing, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
Chronic obstructive pulmonary disease; Cigarette smoke; Animal model; Morphometry; Pulmonary function; Rats; INDUCED EMPHYSEMA; N-ACETYLCYSTEINE; MUCIN SECRETION; INFLAMMATION; CELLS; MICE; DIAGNOSIS; AIRWAYS; TISSUE; MUCUS;
D O I
10.1016/j.toxlet.2009.06.850
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
Cigarette smoke (CS) induced chronic obstructive pulmonary disease (COPD) has been emerging as a great health problem in China. However, lack of appropriate animal model slows down the progress in understanding pathogenesis of the disease. The aim of current study is to establish and evaluate a more adequate rat model of COPD. Study was performed with rats exposed to sidestream cigarette smoke 2 h/d and 7 d/wk for 2, 4, 6, 8, 10, 12, 24 and 36 wk in a CS chamber (carbon monoxide concentration was 231 +/- 11 ppm). The lung function was determined by using the forced oscillation technique. Pathologic changes were determined by using histological analyses and mucin measurement. Following 36-wk exposure, airway resistance (Raw) and respiratory system elastance (Ers) in CS group rats was elevated by 28.5% and 37.5%, respectively. Up to 4.1-, 2.3- and 1.4-fold increase in the number of neutrophils, macrophages and lymphocytes was observed in the BALF of CS rats. Using quantitative histomorphology techniques, it was found that mean linear intercept (MLI) and mean alveolar airspace (MAA) of CS rats increased by 44.8% and 43.7%, respectively, indicating the occurrence of emphysema. The characteristics of chronic bronchitis including hyperplasia of bronchial epithelial cells, hypersecretion of mucus and development of peribronchial fibrosis were also found in rat lungs. CS group rats showed 43% body weight gain reduction. To conclude, a more adequate sidestream cigarette smoke rat COPD model was established, which will be beneficial for understanding the pathogenesis of the disease and for evaluation of drug effectiveness. (c) 2009 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:225 / 234
页数:10
相关论文
共 38 条
  • [1] P-2u purinoceptor regulation of mucin secretion in SPOC1 cells, a goblet cell line from the airways
    Abdullah, LH
    Davis, SW
    Burch, L
    Yamauchi, M
    Randell, SH
    Nettesheim, P
    Davis, CW
    [J]. BIOCHEMICAL JOURNAL, 1996, 316 : 943 - 951
  • [2] Systemic effects of chronic obstructive pulmonary disease
    Agustí, AGN
    Noguera, A
    Sauleda, J
    Sala, E
    Pons, J
    Busquets, X
    [J]. EUROPEAN RESPIRATORY JOURNAL, 2003, 21 (02) : 347 - 360
  • [3] Agusti Alvar, 2007, Proc Am Thorac Soc, V4, P522, DOI 10.1513/pats.200701-004FM
  • [4] MORPHOMETRIC ANALYSIS OF INTRALUMINAL MUCUS IN AIRWAYS IN CHRONIC OBSTRUCTIVE PULMONARY-DISEASE
    AIKAWA, T
    SHIMURA, S
    SASAKI, H
    TAKISHIMA, T
    YAEGASHI, H
    TAKAHASHI, T
    [J]. AMERICAN REVIEW OF RESPIRATORY DISEASE, 1989, 140 (02): : 477 - 482
  • [5] [Anonymous], 1999, AM J RESP CRIT CARE, V159, pS1
  • [6] α-tocopherol and ascorbic acid supplementation reduced acute lung inflammatory response by cigarette smoke in mouse
    Bezerra, Frank Silva
    Valenca, Samuel Santos
    Lanzetti, Manuella
    Pimenta, Wagner Alves
    Castro, Paulo
    Goncalves Koatz, Vera Lucia
    Porto, Luis Cristovao
    [J]. NUTRITION, 2006, 22 (11-12) : 1192 - 1201
  • [7] Cigarette smoke-induced pulmonary inflammation and emphysema are attenuated in CCR6-deficient mice
    Bracke, Ken R.
    D'hulst, An I.
    Maes, Tania
    Moerloose, Katrien B.
    Demedts, Ingel K.
    Lebecque, Serge
    Joos, Guy F.
    Brusselle, Guy G.
    [J]. JOURNAL OF IMMUNOLOGY, 2006, 177 (07) : 4350 - 4359
  • [8] Standards for the diagnosis and treatment of patients with COPD: a summary of the ATS/ERS position paper
    Celli, BR
    MacNee, W
    Agusti, A
    Anzueto, A
    Berg, B
    Buist, AS
    Calverley, PMA
    Chavannes, N
    Dillard, T
    Fahy, B
    Fein, A
    Heffner, J
    Lareau, S
    Meek, P
    Martinez, F
    McNicholas, W
    Muris, J
    Austegard, E
    Pauwels, R
    Rennard, S
    Rossi, A
    Siafakas, N
    Tiep, B
    Vestbo, J
    Wouters, E
    ZuWallack, R
    [J]. EUROPEAN RESPIRATORY JOURNAL, 2004, 23 (06) : 932 - 946
  • [9] Effect of an MMP-9/MMP-12 inhibitor on smoke-induced emphysema and airway remodelling in guinea pigs
    Churg, Andrew
    Wang, Rona
    Wang, Xiaoshan
    Onnervik, Per-Ola
    Thim, Kerstin
    Wright, Joanne L.
    [J]. THORAX, 2007, 62 (08) : 706 - 713
  • [10] Cukic Vesna, 2007, Med Arh, V61, P175