A mucoactive drug carbocisteine ameliorates steroid resistance in rat COPD model.
Pulm Pharmacol Ther
; 39: 38-47, 2016 08.
Article
em En
| MEDLINE
| ID: mdl-27328977
ABSTRACT
Steroid insensitivity has been commonly found in chronic obstructive pulmonary disease (COPD) patients, which is mediated by the reduction of histone deacetylase (HDAC) 2. Here we aimed to establish a steroid resistant model on experimental COPD rats and evaluate the effect of carbocisteine (S-CMC), a mucoactive drug. Exposure to cigarette smoke (CS) caused marked pathological features of COPD which are insensitive to DEX associated with the down-regulation of HDAC2 expression/activity. The DEX insensitivity observed in COPD featured rats was improved by S-CMC in the aspects of inhibiting chronic lung inflammation (total and differential inflammatory cell counts, inflammatory cytokines release and inflammatory cells infiltration); ameliorating airway remodeling (thickness of airway epithelium and smooth muscle, airway fibrosis, and the level of α-SMA and TGF-ß1); improving emphysema (emphysema index D2, level of MMP-9 in BALF and the expression of alpha-1 antitrypsin) and preventing impairments of lung function (PEF, IP and IP-slope). Simultaneously, down-regulation of HDAC2 expression/activity was ameliorated by S-CMC treatment. These results indicate that the rat COPD model with steroid resistance was established by active smoking in a short time frame and demonstrate that the failure of steroid therapy can be restored by S-CMC accompanied by increasing HDAC2 expression/activity, providing additional evidence that S-CMC might be used for GC resistance in COPD.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Dexametasona
/
Carbocisteína
/
Doença Pulmonar Obstrutiva Crônica
/
Expectorantes
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Pulm Pharmacol Ther
Assunto da revista:
FARMACOLOGIA
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
China