Abstract:

Objective To explore the effect of chymase inhibitor on bleomycin-induced pulmonary fibrosis and chymase mRNA and transforming growth factor-β1 (TGF-β1) mRNA expressions in rats. MethodsSixty female rats were randomly divided into three groups: the model group, the control group and chymase inhibitor(Chy-I) treatment group in which the rats were intratracheally instilled with 5?mg/kg bleomycin. From the first day after bleomycin challenge, every day, in the chymase inhibitor treatment group 10mg/kg chymase inhibitor was perfused into the stomach, and the other groups were given sterile saline. Five rats were killed in each group on the 7th, the 14th, the 21st day and the 28th day. The pathological changes of lung tissues and the total and different white blood cells of bronchoalveolar lavage fluid(BALF) were determined by hematoxylin-eosin staining. mRNA expressions of chymase and TGF-β1 in pulmonary tissues were determined by reversal transcription-polymerase chain reaction(RT-PCR). Results  ① Alveolitis in the model and the Chy-I groups were significantly lower than in the control group, but there was no significant different between the model and the Chy-I groups.②　Pulmonary fibrosis was evidently inhibited afterchymase inhibitor treatment. ③ Total white blood cells and percentage of macrophages, lymphocyte and neutrophils in BALF were significantly increased in the model group and the Chy-I group as compared with the control group. On the 7th and 14th days, neutrophils was significant increased in the Chy-I group as compared with the model group. ④　mRNA expression levels of chymase and TGF-β₁ were evidently inhibited after chymase inhibitor treatment, and they were higher in the lung fibrosis of the model group than in the control group, also they were significantly lower in the Chy-I group than in the model group. ConclusionChymase inhibitor can alleviate bleomycin-induced pulmonary fibrosis in rats by inhibiting mRNA expressions of chymase and TGF-β1 in lung tissues.

Key words: Pulmonary fibrosis; Chymase; Transforming growth factor beta; Rats, SpragueDawley