Aim: To investigate the effect of aerosolized signal transducer and activator of transcription 1 (STAT1) antisense oligodeoxynucleotides (ASON) on the expression of inflammatory mediators in bronchoalveolar lavage fluid (BALF) and typeI and typeIII collagen mRNA of the bleomycin-induced rat pulmonary fibrosis.
Methods: 45 adult female Wistar rats were randomly divided into 3 groups: normal saline (NS) group, bleomycin (BLM) group and ASON group. BLM group and ASON group were intratracheally instilled with bleomycin (BLM) while NS group was instilled with NS. NS group and BLM group were aerosolized with NS while ASON group was aerosolized with STAT1 ASON on day 0, 2, 4 and 6 after intratracheal administration. Then each group was divided into 3 subgroups and the rats were sacrificed on day 7, 14 and 28. The concentration of IFN-gamma, TNF-alpha, TGF-beta1 and PDGF-BB in BALF was detected. The lung tissues were removed and HE and Masson staining was performed to observe the extent of alveolitis and fibrosis. The mRNA levels of typeI and typeIII collagen in the lung tissues were measured.
Results: Compared with BLM group, the scores of alveolitis and fibrosis in ASON group were remarkably meliorated (P<0.05). Compared with NS group, the concentration of TNF-alpha, TGF-beta1 and PDGF-BB in BALF in BLM group was significantly increased, but it was lower in ASON group than in BLMA group (P<0.05). The concentration of IFN-gamma in BALF was lower in BLM group than in NS group (P<0.05), but it was higher in ASON group than in BLM group (P<0.05). The mRNA levels of typeI and typeIII collagen at various time points in ASON group were significantly lower than those in BLM group (P<0.05).
Conclusion: The aerosolized STAT1 ASON has anti-fibrosis effect, which may result from the lessened production of typeI and typeIII collagen through reducing the concentration of cytokines in BALF such as TNF-alpha, PDGF-BB and TGF-beta1 and inhibiting the decline of IFN-gamma in BALF.