[The expression of transforming growth factor beta-1 in rat model of chronic obstructive pulmonary disease and the effects of early drugs intervention].
To evaluate the expression of transforming growth factor beta-1(TGF-beta1) and the effects of early drugs intervention of chronic obstructive pulmonary disease(COPD) in rat model.



The COPD rat model (group B) was established by intratracheal instillation of lipopolysaccharide twice and daily exposure to cigarette smoking. Drug intervention groups received dongchongxiacao orally daily from the three days before the experiment (group C) and erythromycin by intraperitoneal injection since the third week (group D)and inhalation of budesonide since the forth week (group E). At the end of 10 weeks, all 40 rats including normal control (group A) were assessed for lung resistance (RL) and dynamic lung compliance (Cdyn). The expression of TGF-beta1 gene and protein were also observed by immunohistochemistry and semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR), respectively.



The changes of pathology and pathophysiology in rat COPD model were similar to those of human COPD. There was a significant increase in the smooth muscle and collagen thickness in the airway wall of the group B in comparison with that of the group A. RL in group B was significantly higher than that in group A (P<0.01), while it was inhibited by early drugs intervention (P<0.01). Cdyn was decreased in group B as compared with that in group A, which was limited by erythromycin and budesonide intervention (P<0.01). The relative content for TGF-beta1 was significantly increased in the epithelial cells of the bronchi, endothelial cells of the pulmonary small vessel and alveolar macrophages of COPD group as compared with those of normal controls (P<0.01).The relative contents for TGF-beta1 in the epithelial of bronchi in group D and group E were significantly lower than that in group B, but not found in group C. There was no difference between group D and group E. There were statistical positive relationships between the RL and the relative content for TGF-beta1 in the bronchial epithelial cells, between the RL and the mRNA level of TGF-beta1 in the lung tissue (P<0.01 approximately 0.05).



This rat COPD model could be helpful to obtain more information about airway remodeling. TGF-beta1 may play an important role during the process of airway remodeling, and could be influenced by early drugs intervention such as budesonide and erythromycin, which may imply their potency in the treatment of COPD. But there is not same phenomenon found in dongchongxiacao group.
Wu
Ding-qian
DQ
Department of Respiratory Medicine, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310009, China.
Liu
Jing
J
Lu
Xiao-yong
XY
Shen
Hua-hao
HH
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D019819:Budesonide / Q000494:pharmacology*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004917:Erythromycin / Q000494:pharmacology*; D008297:Male; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics; D053773:Transforming Growth Factor beta1
D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D004365:Drugs, Chinese Herbal; D012333:RNA, Messenger; C508960:TGFB1 protein, human; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D019819:Budesonide; D004917:Erythromycin