| Background Chronic obstructive pulmonary disease (COPD) is a disease state characterized by airflow limitation that is not fully reversible. The airflow limitation is usually both progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases. It is a major public health problem. It is the fourth leading cause of chronic morbidity and mortality in the United States and is projected to rank fifth in 2020 as a worldwide burden of disease according to a study published by the World Bank/World Health Organization. The pathogenesis of COPD is hitherto not complete clear. The irreversible component of airflow limitation is primarily due to remodeling of the small airways. Airway wall remodeling refers to: hypertrophy of submucosal mucus-secreting glands, epithelial mucous metaplasia, subepithelial fibrosis, bronchiolar smooth muscle hyperplasia, excessive deposition of extracellular matrix and so on. Generally, the remodeling process is responsible for chronic inflammatory and immoderate repair interaction. Transforming growth factor- 1(TGF- l)appears to play an integral role in promoting the structural changes of airway remodeling. To develop a new animal model of COPD is important for hypothesis testing regarding pathogenetic mechanisms of COPD. We try to establish a rat model with COPD airway remodeling processes on the basis of previous described method. Theoretically, remodeling can be arrested by anti-inflammatory drug viainhibit inflammation process. Inhaled corticosteroid might limit the thickening of basement membrane in asthma animal. But it is uncertain on COPD. Newly studies demonstrate that erythromycin has anti-fibrosis, anti-inflammatory function, and also little research investigate the effect on COPD. Additionally, we have observed the anti-inflammatory effect of dongchongxiacao and whether it affect airway remodeling or not need to advanced study.Objective To develop a COPD model for facilitating detailed study of airway remodeling, and to observe the expression of TGF- P 1 in lung. Than to investigate the effect of drugs intervention on airway remodeling and expect to offer useful information for their clinic therapy.Methods All forty male SD rats were offered by animal experimental center of zhejiang province. Rats randomly divided five groups. The COPD rat model (group B) was established by intratracheal instillation of lipopolysaccharide twice and daily exposure to cigarette smoking. Drug intervention groups received daily dongchongxiacao(group C) orally from the three days before the experiment and erythromycin(group D) by intraperitoneal injection since the third week and inhalation of budesonide(group E) since the forth week. At the end of ten weeks, all rats included normal control (group A) were assessed in terms of lung resistance(RL) and dynamic lung compliance(Cdyn),also the protein and gene relative content of TGF-. Ion bronchopulmonary as well as the effects of drugs were observed by immunohi.Uochemistry and semi-quantitative reverse transcription-polymerase chain reactkm(RT-PCR).Animal left lungs were prepared to stain with hematoxylin and eosin to assess the inflammatory cell infiltrate, Masson's trichrome to determine collagen deposition in the lungs after fixing with an intratracheal infusion of 10% formalin at a pressure of 25cmH2O for 0.5 hour. Some right lungs were prepared to determinate protein and hydroxypronline content. Partial lungs were examined with electron microscope. The following morphmetric parameters with a computerized image analysis system (LEICA, Germany) were measured in all airways cut in reasonable cross-sections (defined by a ratio of minimal I.D. to maximal I.D. of lessthan 0.5): the length of the basement membrane of the epithelium (Pbm), the outer adventitial perimeter (Po),and the areas of airway wall (Wat=Ao-Abm) and collagen (WAc). The airways were divided into three categories according to the length of thei... |
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