Abstract | BACKGROUND AND OBJECTIVE: The role of apoptosis in lung destruction in emphysema/ COPD is increasingly being recognized. The relationship between anti-oxidants and alveolar septal cell apoptosis in COPD lungs remains to be elucidated. The aim of this study was to investigate the effects of the anti-oxidant, N-acetylcysteine (NAC), on the development of emphysema and alveolar septal cell apoptosis in smoking-induced COPD in rats. METHODS: Sprague-Dawley rats (n = 48) were randomly assigned to normal, COPD, sham and NAC groups. The effects of treatment were assessed by measuring the levels of vascular endothelial growth factor ( VEGF) in BAL fluid by ELISA, VEGF and VEGF receptor-2 (VEGFR2) protein expression by western blotting, and the apoptotic index (AI) of alveolar septal cells by terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) assay. Histopathological evaluations (mean linear intercept (MLI), destructive index (DI)) and lung function measurements were performed. RESULTS: FEV(0.3)/FVC and PEF were lower in the COPD group than in the normal group. MLI and DI were lower in the NAC-treated group than in the COPD or sham-treated groups. As confirmed by western blotting, the levels of VEGF in BAL fluid were higher in the NAC-treated group than in the COPD group. VEGFR2 protein expression was higher in the NAC-treated group than in the COPD group. The AI was significantly lower in the NAC-treated group than in the COPD group. There was an inverse correlation between levels of VEGF in BAL fluid and the AI of alveolar septal cells. CONCLUSIONS: NAC attenuates lung damage, pulmonary emphysema and alveolar septal cell apoptosis by partly reversing the decrease in VEGF secretion and VEGFR2 protein expression in smoking-induced COPD in rats.
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Authors | Shan Cai, Ping Chen, Cheng Zhang, Jian-Bo Chen, Jie Wu |
Journal | Respirology (Carlton, Vic.)
(Respirology)
Vol. 14
Issue 3
Pg. 354-9
(Apr 2009)
ISSN: 1440-1843 [Electronic] Australia |
PMID | 19341424
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antioxidants
- Vascular Endothelial Growth Factor A
- Acetylcysteine
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Topics |
- Acetylcysteine
(administration & dosage, pharmacology, therapeutic use)
- Administration, Oral
- Animals
- Antioxidants
(administration & dosage, pharmacology, therapeutic use)
- Apoptosis
(drug effects)
- Bronchoalveolar Lavage Fluid
- Disease Models, Animal
- Male
- Pulmonary Alveoli
(drug effects, pathology, physiopathology)
- Pulmonary Disease, Chronic Obstructive
(drug therapy, pathology, physiopathology)
- Pulmonary Emphysema
(drug therapy, pathology, physiopathology)
- Rats
- Rats, Sprague-Dawley
- Smoking
(adverse effects)
- Vascular Endothelial Growth Factor A
(metabolism)
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