[A study on pathological changes and the potential role of growth factors in the airway wall remodeling of COPD rat models].
OBJECTIVE
To study the pathological features of the smooth muscles and collagen in small airways of the COPD rat models and their roles in the airway obstruction, to evaluate the relationship between TGF-beta(1), EGF and bFGF and the airway wall remodeling.


METHODS
Rat COPD model (model group) was established by intratracheal instillation of lipopolysaccharide (LPS 200 microgram/200 microL) twice and exposure to cigarette smoke daily. Drug intervention groups received either daily inhalation of budesonide, ipratropine or heparin respectively, starting on the 8 th day or TGF-beta(1) monoclonal antibody (TB21) 0.5 mg twice (6 th and 19 th day) via the tail veinous injection. At the end of four weeks, the thickness of the smooth muscles and collagen in bronchi and pulmonary arteriole wall were measured by means of image analyzer (CMIAS). Expression and localization of the 3 growth factors were observed in trachea, bronchi and lung tissues by immunohistochemistry and in situ hybridization. The levels of PC III, Ln and HA in the serum and BALF were determined by the RIA method.


RESULTS
Significant thickening of the smooth muscles and collagen were found in the bronchi and pulmonary arterioles of the model group in comparison with those of the control group. There was significant decrease in the thickness of the collagen and smooth muscles in the small airways in TB21 group and heparin group. Statistically negative relationships were shown between the thickness of either smooth muscles or collagen in the small airways and FEV(0.3) (all P < 0.05). The levels of PC III, Ln and HA in COPD rat models were higher than those of control groups to varying extent. Expressions of TGF-beta(1), EGF and bFGF in the epithelial cells of bronchi, endothelial cells of pulmonary arterioles and in the macrophages of the model group were significantly higher than those of control group. The above mentioned parameters were reduced in different extent in drug intervention groups, in particular, the smooth muscles thickness in heparin group and the collagen thickness in TB21 group were significantly decreased compared to the model group.


CONCLUSIONS
Thickening of smooth muscles and collagen in the bronchi constitutes the fundamental pathology of airway remodeling in the rat COPD model. The excessive depositions of ECM are important characteristics of COPD. TGF-beta(1), EGF and bFGF may play an important role in the airway wall as well as pulmonary arteriole remodeling. The intervention against TGF-beta(1) and long term inhalation of heparin may be of use in the inhibition of airway remodeling in COPD.
Song
Y
Y
The 304th Hospital of PLA, Beijing 100037, China.
Cui
D
D
Mao
P
P
D000818:Animals; D001160:Arterioles / Q000378:metabolism / Q000473:pathology*; D001980:Bronchi / Q000378:metabolism / Q000473:pathology*; D001992:Bronchoalveolar Lavage Fluid; D024061:Collagen Type III / Q000378:metabolism; D004195:Disease Models, Animal; D004815:Epidermal Growth Factor / Q000235:genetics / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000098:blood supply / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D053773:Transforming Growth Factor beta1
D024061:Collagen Type III; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D016222:Fibroblast Growth Factor 2; D004815:Epidermal Growth Factor