[Therapeutic effects of aerosolized signal transducer and activator of transcription 1 antisense oligonucleotide administered at different time points on bleomycin-induced pulmonary fibrosis: experiment with rats].

OBJECTIVE

To investigate the curative effects of inhaling signal transducer and activator of transcription 1 (STAT1) antisense oligonucleotide (ASON) on alveolitis and pulmonary fibrosis and the best administration time.

METHODS

Twenty-five adult female Wistar rats were randomly divided into 5 equal groups: BLM group, undergoing intra-tracheal perfusion of BLM so as to establish animal models of alveolitis and pulmonary fibrosis and then inhaling aerosolized normal saline (NS); NS group undergoing intra-tracheal perfusion of NS and then inhaling aerosolized NS; ASON 0 d group, undergoing intra-tracheal perfusion of BLM and then inhaling aerosolized STAT1 ASON 3 ml immediately; ASON 7 d group, undergoing intra-tracheal perfusion of BLM and then inhaling STAT1 ASON 3 ml 7 days later; and ASON 14 d group undergoing intra-tracheal perfusion of BLM and then inhaling aerosolized STAT1 ASON 3 ml 14 days later. Aerosolized inhalation was repeated once every other day for 4 times. Twenty-eight days after intra-tracheal perfusion the rats were sacrificed with their lungs taken out to undergo pathological examination. NS was infused into the right lungs to get bronchoalveolar lavage fluid (BALF). ELISA was used to examine the concentrations of transforming growth factor-beta (TGF-beta) and tumor necrosis factor-alpha (TNF-alpha) in the BALF.

RESULTS

The pathology result of the lung tissues showed that compared with the BLM and ASON 14 d groups, the alveolitis and pulmonary fibrosis of the ASON 0 d group were obviously milder. The scores of alveolitis and pulmonary fibrosis of the ASON 0 d group were (1.80 +/- 0.84) and (2.60 +/- 0.55) respectively, both significantly lower than those of the BLM group [(2.40 +/- 0.55) and (4.40 +/- 0.55) respectively] and those of the ASON 7 d group [(2.20 +/- 0.45) and (3.00 +/- 0.71) respectively] (all P < 0.05). The scores of pulmonary fibrosis of the ASON 7 d group was significantly lower than those of the BLM and ASON 14 d groups (both P < 0.05). The concentrations of TGF-beta and TNF-alpha in BALF of the ASON 0 d group were (48.11 +/- 3.46) pg/ml and (1.93 +/- 0.14) ng/ml respectively, both significantly lower than those of the BLM group [(57.67 +/- 2.46) pg/ml and (2.45 +/- 0.25) ng/ml respectively, both P < 0.05]. The concentration of TGF-beta in BALF of the ASON 0 d group was significantly lower than those of the ASON 7 d and ASON 14 d groups [(51.42 +/- 3.57) pg/ml and (55.8 3 +/- 1.79) pg/ml respectively, both P < 0.05]. The concentration of TGF-beta in BALF of the ASON7 d group was significantly lower than those of the BLM and ASON 14 d groups (both P < 0.05).

CONCLUSIONS

STAT1 ASON administered in the early stage helps depress the pulmonary fibrosis procedure, and the earlier the drug is administrated the better effect would be obtained. Aerosolized STAT1 ASON can be used as a therapeutic method for pulmonary fibrosis.