Study On The Effect Of Chymase Inhibitor On The Rat Model Of Bleomycin-Induced Pulmonary Fibrosis

Objective:To study the effect of chymase inhibitor on bleomycin-induced pulmonary fibrosis in rats and its possible mechanism.Methods:Sixty female were randomly divided into three groups:the model group, the control group and chymase inhibitor treatment group,in which the rats were intratracheally instilled with(5mg/kg)bleomycin.From the first day after bleomycin challenge,by every day,the chymase inhibitor treatment group was perfused into stomach daily chymase inhibitor(10mg/kg),the other group were given sterile saline. Five rats were killed each group respectively at the time of the seventh day,the fourteenth day,the twenty-first day and the twenty-eighth day.The pathological changes of lung tissue by hematoxylin-eosin staining were investigated.The total and different white blood cells,The mRNA expression of chymase,TGF-β₁ in pulmonary tissue were analyzed by using the reversal transcription-polymerase chain reactionl(RT-PCR). The level of transforming growth factor-β1(TGF-β₁)in the bronchoalveolar lavage fluid(BALF)was tested by Enzyme-linked Immuno Sorbent Assay(ELISA).The expression of TGF-β₁,collagenâ… ,collagenâ…¢,angiotensinâ…¡and AT1-receptor in lung tisusue were examined by immuohistochemical analysis.Results:Alveolitis in the model group and Chy-â… group were significantly higher as compared with the control,level of pulmonary fibrosis as inhibited evidently after the treatment by chymase inhibitor.Significant increase in total white blood cells and percentage of macrophages,lymphocyte and neutrophils in BALF was found in the model group and the Chy-â… group as compared to the control group.In the seventh and fourteenth day,Significant increase in neutrophils was found in the the Chy-â… group as compared to model group.The level of TGF-β₁ in BALF as inhibited evidently after the treatment by chymase inhibitor.The expression of TGF-β₁,collagenâ… ,collagenâ…¢angiotensinâ…¡and AT1-receptoin the lung fibrosis of BLM group was higher than in control group with significant difference,and treatment group was lower than BLM group with significant difference.Conclusion:chymase inhibitor can alleviated BLM induced pulmonary fibrosis in rat,inhibiting the expression of TGF-β₁,collagenâ… ,collagenâ…¢,angiotensinâ…¡and AT1-receptor in lung tissue maybe one of the mechanisms.