[The potential role of growth factor in the airway wall remodeling of a chronic obstructive pulmonary disease rat model and the effects of drugs on them].
OBJECTIVE
To evaluate the expression and distribution of transforming growth factor-beta1 (TGF-beta1), epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) in the lung tissue of chronic obstructive pulmonary (COPD) rat models and the relationship between these growth factors and the airway wall remodeling. The effects of drugs on them were also investigated.


METHODS
The COPD rat model (model group) was established by intratracheal instillation of lipopolysaccharide twice and daily exposure to cigarette smoking. Drug intervention groups received daily inhalation of heparin since the second week and TGF-beta1 monoclonal antibody (TB21) 0.5 mg twice through the tail veins. At the end of four weeks, the thickness of the smooth muscle and collagen in bronchi and pulmonary arterioles were measured by computer image analyzer, also the protein and gene relative content of these growth factors as well as the effects of drugs on them were observed.


RESULTS
There was a significant increase in the smooth muscle and collagen thickness in the bronchi and pulmonary arterioles of the model group in comparison with that of the control group (P < 0.01), the relative contents for TGF-beta1, EGF and bFGF in the epithelial cells of the bronchi, endothelial cells of the pulmonary arterioles and alveolar macrophages of the model group were significantly higher than those of control group (P < 0.001 approximately 0.05). The relative content for TGF-beta1 in TB21 group was significantly lower than that of model group (P < 0.01). These were statistical positive relationships between the smooth muscle e thickness of bronchi and the relative contents for TGF-beta1, EGF and bFGF in the epithelial cells, between the collagen thickness of the bronchi and the relative content for TGF-beta1, between the smooth muscle thickness of the pulmonary arterioles and the relative content for TGF-beta1 and EGF in the endothelial cells (P < 0.05 approximately 0.01).


CONCLUSIONS
TGF-beta1, EGF and bFGF may play an important role in the airway wall and pulmonary arteriole structure remodeling in COPD, the intervention against TGF-beta1 and long term inhalation of heparin mat be helpful for the inhibition of airway wall remodeling in human COPD and worth of further observation.
Song
Y
Y
Department of Respiratory Medicine, The 304th Hospital of PLA, Beijing 100037, China.
Cui
D
D
Mao
P
P
D000818:Animals; D001980:Bronchi / Q000473:pathology*; D004195:Disease Models, Animal; D004815:Epidermal Growth Factor / Q000096:biosynthesis* / Q000502:physiology; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis* / Q000502:physiology; D006493:Heparin / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000502:physiology
D008070:Lipopolysaccharides; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2; D004815:Epidermal Growth Factor; D006493:Heparin